Type Of Soft Tissue Sarcoma Research Articles

Profiling the cancer-prone microenvironment in a zebrafish model for MPNST.

Microenvironmental contributions to soft tissue sarcoma progression are relatively undefined, particularly during sarcoma onset. Use of animal models to reveal these contributions is impeded by difficulties in discriminating between microenvironmental, precancerous, and cancer cells, and challenges in defining a precancerous microenvironment. We developed a zebrafish model that allows segregation of microenvironmental, precancerous, and cancerous cell populations by fluorescence-activated cell sorting. This model has high predilection for malignant peripheral nerve sheath tumor (MPNST), a type of soft tissue sarcoma that exhibits rapid, aggressive growth. Using RNA-seq, we profiled the transcriptomes of microenvironmental, precancerous, and cancer cells from our zebrafish MPNST model. We show broad activation of inflammation/immune-associated signaling networks, describe gene expression patterns that uniquely characterize the transition from precancerous to cancer ME, and identify macrophages as potential contributors to microenvironmental phenotypes. We identify conserved gene expression changes and candidate genes of interest by comparative genomics analysis of MPNST versus benign lesions in both humans and zebrafish. Finally, we functionally validate a candidate extracellular matrix protein, periostin (POSTN), in human MPNST. This work provides insight into how the microenvironment may regulate MPNST initiation and progression.

Histology-Tailored Approach to Soft Tissue Sarcoma.

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.

A phase II, open-label, single-arm trial of pembrolizumab for recurrent meningioma and solitary fibrous tumor.

Atypical and anaplastic meningiomas account for 20% of all meningioma cases. Solitary fibrous tumor (SFT) is a type of soft tissue sarcoma with similar attributes to meningioma. For patients with refractory or recurrent disease after previous surgery or radiotherapy, there is no effective treatment. Pembrolizumab, an anti-programmed cell death 1 (PD-1) antibody, is an effective treatment for various solid tumors. PD-1 ligand is highly expressed in aggressive meningiomas. We aimed to assess the effectiveness of pembrolizumab in treating meningioma and SFT recurrence after surgery and radiation therapy. This prospective single-arm phase II trial comprised 15 patients with recurrent meningioma and 3 with anaplastic SFT, treated at a single institution during 2018 to 2022. The study was terminated due to a lack of efficacy and slow accrual. The primary endpoint was 6-month progression-free survival (PFS-6). Median progression-free survival (PFS) was 2.6 months, and median overall survival (OS) was 40 months. The 6- and 12-month PFS were both 11.1%. The 6- and 12-month OS were 94.4% and 61.1%, respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the overall response rate was 11%, with 2 patients achieving stable disease and 2 with partial response. Three patients (16.7%) developed grade 3 toxicity. Our results showed that pembrolizumab failed to improve PFS-6 in patients with aggressive meningioma or anaplastic SFT. However, two patients, one with atypical meningioma and one with anaplastic SFT, achieved a partial response. More clinical studies are needed to identify which subset of patients may benefit from this treatment.

Segmentation model of soft tissue sarcoma based on self-supervised learning.

Soft tissue sarcomas, similar in incidence to cervical and esophageal cancers, arise from various soft tissues like smooth muscle, fat, and fibrous tissue. Effective segmentation of sarcomas in imaging is crucial for accurate diagnosis. This study collected multi-modal MRI images from 45 patients with thigh soft tissue sarcoma, totaling 8,640 images. These images were annotated by clinicians to delineate the sarcoma regions, creating a comprehensive dataset. We developed a novel segmentation model based on the UNet framework, enhanced with residual networks and attention mechanisms for improved modality-specific information extraction. Additionally, self-supervised learning strategies were employed to optimize feature extraction capabilities of the encoders. The new model demonstrated superior segmentation performance when using multi-modal MRI images compared to single-modal inputs. The effectiveness of the model in utilizing the created dataset was validated through various experimental setups, confirming the enhanced ability to characterize tumor regions across different modalities. The integration of multi-modal MRI images and advanced machine learning techniques in our model significantly improves the segmentation of soft tissue sarcomas in thigh imaging. This advancement aids clinicians in better diagnosing and understanding the patient's condition, leveraging the strengths of different imaging modalities. Further studies could explore the application of these techniques to other types of soft tissue sarcomas and additional anatomical sites.

Analysis of demographic and socioeconomic factors in biphasic synovial sarcoma using data from the National Cancer Database.

e23524 Background: Synovial sarcoma, a rare type of soft tissue sarcoma, can be classified into two subtypes - biphasic and spindle cell. Of the two, biphasic synovial sarcoma (BSS) has a better 5-year survivorship; however, 35% of patients diagnosed with BSS die within 5 years. Despite past controversy, adjuvant chemotherapy has been found to improve overall survival for patients with stage III BSS. The National Cancer Database (NCDB) was examined to discover the demographics of individuals diagnosed with BSS. Methods: The 2004-2020 NCDB was analyzed to conduct a retrospective cohort analysis. Patients with a histologically confirmed diagnosis of BSS (ICD-O-3 code 9043) were included (N = 92). Demographic factors like age, sex, race, Hispanic origin, insurance status, educational attainment, distance from facility, facility type, and Charles/Deyo score were evaluated using descriptive statistics and incidence trends were interpreted with regression analysis. Results: Ninety-two biphasic synovial sarcoma cases sampled between 2004 and 2020 revealed an average age at diagnosis of 47.3 years (SD = 19.9, range = 5–87), with males being more likely to be diagnosed (58%). The patients reside at an average of 42 miles from treatment facilities (SD = 108.56, range = 0.3–800.6). Primary disease sites varied, including the lower lobe of the bronchus or lung (12%), upper lobe (11%), and long bones (11%). Diagnosis frequency (2004–2020) showed minimal variation (R^2 = 0.007). Palliative care was not received in 95% of cases, and 41% of patients did not undergo a surgical procedure at the primary site. In patients who received surgery, residual tumor absence post-resection was noted in 56% of patients. Primary treatments included chemotherapy (48%) and radiation therapy (42%), with an average tumor size of 65.2 mm (SD = 42.8, range = 9–195 mm). Notably, 74% survived beyond 90 days post-surgery, with a thirty-day mortality rate of 2%. Patients survived an average of 8.5 years post-diagnosis. Facility-wise, 37% were in academic/research programs. Privately insured patients constituted 60%, with 51% of all patients residing in metropolitan areas of 1 million or more. Conclusions: This analysis addresses a critical knowledge gap, offering insights into the demographics and socioeconomic factors affecting the diagnosis and treatment of Biphasic Synovial Sarcoma (BSS). The average age of BSS diagnosis is 47.3 years with males being predominantly affected, consistent with earlier case reports. BSS patients showed diverse geographic distribution. Survival beyond 90 days post-surgery was high. Chemotherapy and radiation therapy were common treatments. Unique findings include a majority residing in metropolitan areas, and non-academic program treatments. This study underscores the necessity for further research to grasp the impact of these factors on BSS diagnosis, treatment, and overall survival.

Predicting Trabectedin Efficacy in Soft Tissue Sarcoma: Inflammatory Biomarker Analysis.

Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs. We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI=neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors. Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (p<0.001, p=0.008, p=0.027, p=0.013, and p<0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (p=0.007, p=0.008, and p=0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio=2.16, p=0.006). Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.

Myxofibrosarcoma of the Chest Wall Detected on 99mTc-MDP Whole-Body Bone Scan.

Myxofibrosarcoma is a type of soft tissue sarcoma, predominantly characterized by a high propensity for local recurrence, albeit demonstrating a relatively diminished risk for distant metastasis. Its prevalence is notably higher in elderly patients. Here, we present a case of a 73-year-old woman diagnosed with Myxofibrosarcoma. She was subjected to a whole-body bone scan using 99mTc-methylene diphosphonate (MDP) to survey potential bony metastasis. It revealed marked MDP accumulation with peripheral soft tissue uptake in the right lateral chest region of this patient. This imaging phenotype could potentially be attributed to the augmented vascularity within the tumor, a finding that was prominently displayed in this particular case.

Abstract 1097: CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway

Abstract Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-Negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies. CD73 is a 5’ ectonucleotidase that hydrolyzes AMP to adenosine and regulates the purinergic signaling pathway. We found that CD73 is elevated in FN-RMS tumors that express high levels of TWIST2. While high expression of CD73 contributes to the pathogenesis of multiple cancers, its role in FN-RMS has not been investigated. We found that CD73 knockdown decreased FN-RMS cell growth while upregulating the myogenic differentiation program. Moreover, mutation of the catalytic residues of CD73 rendered the protein enzymatically inactive and abolished its ability to stimulate FN-RMS growth. Overexpression of wildtype CD73, but not the catalytically inactive mutant, in CD73 knockdown FN-RMS cells, restored their growth capacity. Likewise, treatment with an adenosine receptor A2A-B agonist partially rescued FN-RMS cell proliferation and bypassed the CD73 knockdown defective growth phenotype. These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients. Citation Format: Karla Gabriela Cano Hernandez, Akansha Shah, Victor Lopez, Vincent Tagliabracci, Kenian Chen, Lin Xu, Rhonda Bassel-Duby, Eric Olson, Ning Liu. CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1097.

Therapeutic approaches for spinal synovial sarcoma: a comprehensive review of the literature.

Synovial sarcoma (SS) is a relatively rare type of soft-tissue sarcoma that is commonly treated with surgery, radiation, chemotherapy, and palliative care. Stereotactic radiosurgery (SRS) is an emerging approach that shows promise in treating CNS conditions, but it has not been studied for SS. The authors present a systematic review that explores the effectiveness of different treatments, with a focus on SRS, for managing spinal SS. A systematic PubMed search was conducted that covered studies from 1964 to 2022, yielding 70 relevant studies. Inclusion criteria encompassed primary and metastatic spinal SS, various treatment modalities, patient age 17 years or older, English-language studies, retrospective series, and case reports. Based on these criteria, 26 studies were included in this review and 44 were excluded. Of the included studies, 15 patients from 9 studies were treated with surgical intervention followed by both conventional radiotherapy (RT) and chemotherapy, 10 patients from 10 studies were treated with surgery followed by RT, 5 studies comprising 8 patients were exclusively treated with surgery, 5 cases in 3 studies were treated with surgery plus concomitant chemotherapy, 4 patients in 2 studies were treated with SRS, and only 1 study reported treatment without surgery and with chemotherapy and RT. The median progression-free survival and overall survival periods observed in the SRS-treated patients were 37 months and 60 months, respectively, which were higher than those of any other treatment method or combination used. The authors' study offers a thorough review of spinal SS treatments. They are hopeful that this will aid clinicians in informed decision-making for better patient outcomes.

Immune evasion in lung metastasis of leiomyosarcoma: upregulation of EPCAM inhibits CD8+ T cell infiltration

BackgroundLeiomyosarcomas are among the most common histological types of soft tissue sarcoma (STS), with no effective treatment available for advanced patients. Lung metastasis, the most common site of distant metastasis, is the primary prognostic factor. We analysed the immune environment targeting lung metastasis of STS to explore new targets for immunotherapy.MethodsWe analysed the immune environment of primary and lung metastases in 38 patients with STS using immunohistochemistry. Next, we performed gene expression analyses on primary and lung metastatic tissues from six patients with leiomyosarcoma. Using human leiomyosarcoma cell lines, the effects of the identified genes on immune cells were assessed in vitro.ResultsImmunohistochemistry showed a significant decrease in CD8+ cells in the lung metastases of leiomyosarcoma. Among the genes upregulated in lung metastases, epithelial cellular adhesion molecule (EPCAM) showed the strongest negative correlation with the number of CD8+ cells. Transwell assay results showed that the migration of CD8+ T cells was significantly increased in the conditioned media obtained after inhibition or knock down of EPCAM.ConclusionsEPCAM was upregulated in lung metastases of leiomyosarcoma, suggesting inhibition of CD8+ T cell migration. Our findings suggest that EPCAM could serve as a potential novel therapeutic target for leiomyosarcoma.

CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high-grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies. CD73 is a 5' ectonucleotidase that hydrolyzes AMP to adenosine and regulates the purinergic signaling pathway. We found that CD73 is elevated in FN-RMS tumors that express high levels of TWIST2. While high expression of CD73 contributes to the pathogenesis of multiple cancers, its role in FN-RMS has not been investigated. We found that CD73 knockdown decreased FN-RMS cell growth while up-regulating the myogenic differentiation program. Moreover, mutation of the catalytic residues of CD73 rendered the protein enzymatically inactive and abolished its ability to stimulate FN-RMS growth. Overexpression of wildtype CD73, but not the catalytically inactive mutant, in CD73 knockdown FN-RMS cells restored their growth capacity. Likewise, treatment with an adenosine receptor A2A-B agonist partially rescued FN-RMS cell proliferation and bypassed the CD73 knockdown defective growth phenotype. These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients.

Surgically Resected Cardiac Angiosarcoma: Survival Analysis from the National Cancer Database.

Angiosarcoma is a rare type of soft-tissue sarcoma arising from endothelial cells. It is considered 'high-grade' by definition, reflecting its aggressive behavior. We sought to investigate the role of surgery in cardiac angiosarcoma, identify late mortality predictors, and identify interactions with other modalities in its treatment using a national dataset. The 2004-2017 National Cancer Database was reviewed for patients with primary cardiac angiosarcoma. Late mortality predictors were evaluated with Kaplan-Meier curves and Cox regression analysis. Surgery in primary cardiac angiosarcoma was performed in 130 patients (median age 50.5 years; female sex 36.9%). The median follow up was 72.02 months, with a median overall survival (OS) of 14.32 months. In patients treated with surgery in combination with other modalities compared with those treated with surgery alone, median OSs were 17.28 and 2.88 months, respectively (log-rank = 0.018). Older patients (age > 57 years) experienced lower OS compared to those with an age < 57 (log-rank = 0.012). This may be partially explained by the difference in treatment strategies among age groups: those with increasing age, less surgery (p = 0.037), and less chemotherapy (p < 0.001) were chosen. With multivariable Cox regression analysis, age and race other than white or black were identified to be significant independent predictors of late mortality. Cardiac angiosarcoma has poor overall survival, and our findings should further encourage the use of surgery in combination with other therapeutic modalities in treating such an aggressive disease whenever possible.

Experimental models of tumor growth in soft tissue sarcomas

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.

GALNT12 promotes fibrosarcoma growth by accelerating YAP1 nuclear localization.

Fibrosarcoma is a highly malignant type of soft tissue sarcoma that currently lacks effective treatment options. Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) belongs to the uridine diphosphate N-acetylgalactosamine gene family, which is involved in numerous biological processes of diseases, such as tumor progression. Its upregulated expression is closely associated with the development of colorectal cancer. However, research on the role of GALNT12 in fibrosarcoma is currently limited. The present study aimed to assess the expression and biological function of GALNT12 in fibrosarcoma. Patient data and tissue samples were collected and public datasets were obtained from the Gene Expression Omnibus (GSE24369 and GSE21124). Immunofluorescence assays were performed to observe the cellular localization of GALNT12. GALNT12 expression was measured using reverse transcription-quantitative PCR, western blotting and immunohistochemistry. Small interfering RNAs were constructed to knock down GALNT12 expression in HT-1080 cells. Cell Counting Kit-8 and EdU assays were used to assess fibrosarcoma cell proliferation. Wound healing and Transwell assays were used to detect migration. Gene set enrichment analysis was performed to identify key pathways. Paired and unpaired Student's t-test, Fisher's exact test and one-way ANOVA (followed by Tukey's Honest Significant Difference test) were used to analyze the data. It was demonstrated that GALNT12 expression was upregulated in both fibrosarcoma cell lines and tissue samples and predicted poor patient prognosis. In vitro experiments demonstrated that high GALNT12 expression levels significantly increased HT-1080 cell proliferation and migration. Furthermore, it was demonstrated that high GALNT12 expression levels were closely associated with the yes1 associated transcriptional regulator (YAP1) signaling pathway. Knockdown of GALNT12 inhibited YAP1 nuclear translocation, which affected activation of key downstream genes including AMOTL2, BIRC5 and CYR61. Therefore, the present study demonstrated that GALNT12 promoted fibrosarcoma progression. GALNT12 could be a potential biomarker for this disease and may potentially provide new ideas for targeted therapy of fibrosarcoma in the future.

Activation of the Akt signalling pathway as a prognostic indicator in canine soft tissue sarcoma

Canine soft tissue sarcoma (STS) is relatively common in dogs and is the generic term for tumours that originate from mesenchymal cells. While histopathological grade and immunolabelling with Ki-67 have been used for estimating prognosis, additional indicators are needed for predicting prognosis. Aberrant cell signalling pathways may contribute to disease activity and, therefore, prognostic markers. However, their role in canine STS remains poorly understood. The aim of this study was to investigate expression of phosphorylated Akt (phospho-Akt) and phosphorylated S6 (phospho-S6) as potential prognostic indicators. Immunohistochemical labelling was conducted on clinical samples of canine STS (n = 67). We found that phospho-Akt expression was positively correlated with histopathological grade (P = 0.001) and Ki-67 index (P <0.01). There was no apparent relationship between the type of STS and the expression of phospho-Akt. The number of cases that expressed phospho-S6, which is the downstream molecule of the Akt signalling pathway, was higher in immunopositive phospho-Akt cases than in immunonegative phospho-Akt cases (P <0.0001). Furthermore, phospho-Akt expression was significantly higher in recurrent and metastatic cases. We also confirmed that phosphorylation of Akt occurred in conjunction with S6 phosphorylation in three canine STS cell lines. These results suggest that immunolabelling for phospho-Akt, phospho-S6 and Ki-67 could potentially be used as a prognostic indicator and therapeutic target in canine STS.

The dynamic contrast enhanced-magnetic resonance imaging and diffusion-weighted imaging features of alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue sarcoma that predominantly affects adolescents and young adults. Early diagnosis of ASPS is crucial for optimal therapeutic planning and improving prognosis, but its diagnostic features are not well delineated. This study aimed to retrospectively analyze the imaging features of ASPS with an emphasis on the dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) findings to identify imaging findings that might suggest the diagnosis to radiologists. The imaging features of 34 patients with pathologically proven limb ASPS were retrospectively analyzed. A total of 23 underwent DCE-MRI, and 12 underwent DWI. Among the 34 cases of ASPS, 31 tumors were in the lower extremities, and 3 were in the upper extremities. The maximum tumor diameters ranged from 3.0 to 19.4 cm (mean, 8.7±3.96 cm). A total of 28 cases had well-defined borders. The masses demonstrated heterogeneous high signal intensity on T2-weighted imaging (T2WI) and the fat-suppressed (FS) T2WI sequence and slight hyperintensity on T1-weighted imaging (T1WI). A total of 25 lesions had thin hypointense bands on T1WI and T2WI. Intra- and peri-tumoral tubular areas of flow void were exhibited on both T1WI and T2WI in all cases. A total of 12 cases showed a high signal on DWI, and the mean apparent diffusion coefficient (ADC) value was (0.86±0.07)×10-3 mm2/s [range, (0.6-1.4)×10-3 mm2/s]. Persistent remarkable enhancement of the lesion was displayed on contrast-enhanced scans. The time-intensity curves (TICs) of 23 masses showed early arterial enhancement and slow washout of contrast. ASPS most commonly presents in the lower extremities of adolescents or young adults. Hyperintense T1WI, T2WI, and DWI signals, low ADC, flow voids, early arterial enhancement are frequent MRI features.

Melanin-targeted [18F]-PFPN PET imaging may shed light for clear cell sarcoma.

Intracytoplasmic melanin pigment is a characteristic of clear cell sarcoma (CCS), which is a particularly deadly type of soft-tissue sarcoma. [18F]-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)picolinamide ([18F]-PFPN) is a positron emission tomography (PET) probe characterized by high melanin affinity. Therefore, this study aimed to investigate the feasibility of melanin-targeted [18F]-PFPN PET in patients with CCS. This prospective single-centre study recruited patients with pathologically confirmed CCS. [18F]-FDG PET/computed tomography and [18F]-PFPN PET/magnetic resonance imaging scans were performed within 1week of each other. The lesion numbers and [18F]-FDG and [18F]-PFPN PET parameters (maximum standardized uptake value [SUVmax], mean standardized uptake value [SUVmean], metabolic/melanotic tumour volume [MTV/MLTV], and total lesion glycolysis/melanin [TLG/TLM]) were collected. Three patients with CCS were recruited and received PET imaging. A total of 56 lesions were detected on [18F]-PFPN PET, including primary tumour and distant metastases. Identical lesions were not detected on [18F]-PFPN and [18F]-FDG PET. Twelve lesions (12/39, 30.77%) on [18F]-FDG imaging were missed on [18F]-PFPN, and 20 lesions (20/47,42.55%) on [18F]-PFPN imaging were missed on [18F]-FDG. In quantitative analysis, the [18F]-FDG SUVmean (4.60 ± 3.24) was higher than the [18F]-PFPN SUVmean (3.0 ± 2.63) in all lesions (P = 0.01). No significant correlations were found between the SUVmax, SUVmean, MLTV/MTV, and TLM/TLG values of [18F]-PFPN and [18F]-FDG (P > 0.05). Melanin-targeted [18F]-PFPN PET imaging is feasible for the diagnosis of CCS. Different imaging features were displayed on [18F]-PFPN and [18F]-FDG PET imaging, demonstrating the complementary role of the tracers. Combined use of the two imaging modalities would be preferred in patients with CCS. NCT05963035.

Effectiveness of tumor‑treating fields to reduce the proliferation and migration of liposarcoma cell lines.

Liposarcoma (LPS) is a rare type of soft tissue sarcoma that constitutes 20% of all sarcoma cases in adults. Effective therapeutic protocols for human LPS are not well-defined. Tumor-treating fields (TTFields) are a novel and upcoming field for antitumor therapy. TTFields combined with chemoradiotherapy have proven to be more effective than TTFields combined with radiotherapy or chemotherapy alone. The present study aimed to assess the effectiveness of TTFields in inhibiting cell proliferation and viability for the anticancer treatment of LPS. The present study used TTFields (frequency, 150 kHz; intensity, 1.0 V/cm) to treat two LPS cell lines (94T778 and SW872) and analyzed the antitumor effects. According to trypan blue and MTT assay results, TTFields markedly reduced the viability and proliferation of LPS cell lines along with the formation of colonies in three-dimensional culture. Based on the Transwell chamber assay, TTFields treatment also markedly reduced the migration of LPS cells. Furthermore, as shown by the higher activation of caspase-3 in the Caspase-3 activity assay and the results of the reactive oxygen species (ROS) assay, TTFields increased the formation of ROS in the cells and enhanced the proportion of apoptotic cells. The present study also investigated the inhibitory effect of TTFields in combination with doxorubicin (DOX) on the migratory capacity of tumor cells. The results demonstrated that TTFields treatment synergistically induced the ROS-induced apoptosis of LPS cancer cell lines and inhibited their migratory behavior. In conclusion, the present study demonstrated the potential of TTFields in improving the sensitivity of LPS cancer cells, which may lay the foundation for future clinical trials of this combination treatment strategy.

Analysis of hospitalizations of patients with Kaposi sarcoma: A national population-based study.

e18821 Background: Kaposi sarcoma (KS) is a type of soft tissue sarcoma due to infection with human herpes virus 8 (HHV-8) and can be associated with acquired immunodeficiency syndrome [AIDS]. Recent national population data are scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with KS in the United States (U.S). Methods: Data were abstracted from the National Inpatient Sample (NIS) Database. This database is the largest collection of inpatient admission data in the U.S. It is a 20-percent stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. The numbers in the databases are weighted to optimize national estimates. Hospitalizations for patients with KS were obtained by searching for hospitalizations that contained ICD-10 code “C46” as a principal or secondary diagnosis. The principal diagnosis is the main reason for the admission, while any other diagnosis other than the principal, are secondary diagnosis. The reason for hospitalization (or principal diagnosis) was recorded in descending order of frequency based on the ICD-10 code organ system category and specific principal diagnosis. The total number of KS discharges, baseline demographic characteristics, hospital length of stay (LOS), and total hospital charges were recorded. STATA 16 was used for analysis. Since NIS contains de-identified data, Institutional Review Board (IRB) review was waived. Results: There were 32 million discharges included in the 2020 NIS database. Of those, 2,785 hospitalizations were for patients aged ≥18 years, who had either a principal or secondary ICD 10 code for KS. Patients were mainly males (91%), black (40%), mean age of 48 years, inpatient mortality of 9.3%, mean LOS of 9 days, and mean total hospital charge of 132,476 U.S dollars. The 5 most common reasons for hospitalization by ICD 10 code categories were infections (52.4%), cardiovascular (6.5%), respiratory (6.1%), neoplasm and hematologic (5.6%), and skin (5.6%). The 5 most common specific principal diagnoses for hospitalizations were Human immunodeficiency virus [HIV] disease (29.1%), sepsis (12.7%), left leg cellulitis (2.7%), pneumonia (2.2%), and Acute kidney injury (1.8%). Conclusions: Hospitalizations for KS patients are mostly black middle-aged men, with high inpatient mortality, long LOS, and significant hospital charges. Infections and HIV were the most common reasons for hospitalizations. Management of underlying HIV and measures for prevention, early detection, and prompt treatment of infections in the outpatient setting are important in preventing hospitalizations of these patients.

Epidemiology, survival, and treatment of liposarcoma subtypes: An analysis of the national cancer database.

e23535 Background: Liposarcomas are a soft tissue sarcoma which grow in adipose tissue, mainly in the subcutaneous fat of the limbs, and are the most common type of soft tissue sarcoma. Relatively little is known about the epidemiology, prevalence, and survival of various histological subtypes of liposarcoma, therefore, in the largest study to date, we analyzed this patient population using the NCDB. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Liposarcoma from 2004 to 2019 using the histology codes 8850, 8851, 8852, 8853, 8855, and 8858 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: We identified 19,351 patients with liposarcoma. Mean age at diagnosis was 59 years for all subtypes and 83.3% of patients were white. Well-differentiated tumors were the most common histological subtype (34.8%), conferred the longest overall survival, and were the largest tumors on average. Round-cell tumors were the rarest (2.4%) and had smaller average tumor size than other subtypes. Patients with the de-differentiated subtype (20.5%) experienced the lowest median survival (70.5 months; p &lt; 0.05) and an increased hazard ratio (HR = 2.8; p &lt; 0.05) after controlling for other subtypes, age, and stage at diagnosis. Surgery was the mainstay of therapy with 90% of patients receiving surgery. 11.2% received additional adjuvant chemotherapy and 2.8% received adjuvant radiotherapy. Round cell and Myxoid tumors were most amenable to resection (89.8% and 88.9% of patients having no residual tumor) compared to only 64.4% of dedifferentiated tumors with complete surgical resection. Conclusions: Liposarcomas are a heterogeneous group of tumors which carry unique patterns of presentation, treatment, and prognosis. Well differentiated tumors are common and amenable to treatment; de-differentiated tumors are more aggressive and remain difficult to fully treat.