Descriptive epidemiology of soft tissue sarcomas and gastrointestinal stromal tumors in Thailand.
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ABSTRACT:
SUBMITTER: Klangjorhor J
PROVIDER: S-EPMC9329344 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesMost epidemiologic studies on soft tissue sarcomas (STS) and bone sarcomas (BS) are performed in western countries, with few in the Middle East and North Africa region. We describe the epidemiology of sarcomas in Lebanon using the medical records database at the American University of Beirut Medical Center (AUBMC).MethodsThis single-center retrospective cohort study included patients with sarcomas registered in the database between 2015 and 2019. Their charts were reviewed for baseline characteristics, tumor biology and location, treatment modalities, recurrence, metastasis, and death.ResultsThe cohort included 234 patients with STS and 99 patients with BS. Most tumors were <10 cm in size. The most common subtypes were liposarcoma for STS and osteosarcoma for BS. The most common location of STS was the thigh. The most frequent sites of STS metastasis were the lungs. Histological subtype, smoking status, and tumor size and grade were significant for progression-free survival (PFS) in patients with STS. By multivariable analysis, smoking was significantly associated with poorer PFS in STS. For BS, only tumor grade was significant for PFS.ConclusionThe epidemiology of sarcomas at AUBMC is similar to that previously reported. Smoking history was associated with poorer survival in patients with STS.
| S-EPMC8918978 | biostudies-literature
Project description:We conducted a retrospective cohort study using data compiled from the regional German cancer registries by the Centre for Cancer Registry Data (ZfKD) at the Robert Koch Institut (RKI) to describe the epidemiology of adult soft-tissue sarcomas (STS) in Germany in 2003-2012, focusing on advanced STS. We identified 33,803 incident adult cases of STS (other than the Kaposi sarcoma and gastrointestinal stromal tumors). The incidence of STS was 6.05 (95% confidence interval (CI), 5.82-6.29) per 100,000 in 2012 (4,079 cases). During 2003-2012, the most common histologic categories were leiomyosarcoma (19%), liposarcoma (16%), and STS not otherwise specified (14%). The overall STS-specific mortality rate in 2012 was 2.31 (95% CI, 2.06-2.57) per 100,000, and the median overall survival from initial diagnosis was 5.83 (95% CI, 5.50-6.08) years. Using STS mortality rates as a proxy for incidence of advanced STS in Germany and applying the age- and sex-specific rates to the corresponding German population, we estimated that 1,581 incident adult advanced STS cases occurred in Germany in 2012. Our findings contribute to a refined understanding of the population burden of STS in Germany, including the number of patients with advanced STS who may be candidates for systemic treatment.
| S-EPMC5904765 | biostudies-literature
Project description:Heat shock protein 90 (HSP90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFR?) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase I study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective HSP90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS).IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m(2) twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging.Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m(2) twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26 of 37) of patients with GIST and 59% (10 of 17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11 of 29 (38%) patients with GIST.In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of antitumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy.
| S-EPMC4330562 | biostudies-literature
Project description:Activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is well documented for a broad spectrum of human malignancies supporting their growth and progression. Accumulating evidence has also implicated AKT as a potent modulator of anti-cancer therapies via regulation of DNA damage response and repair (DDR) induced by certain chemotherapeutic agents and ionizing radiation (IR). In the present study, we examined the role of AKT signaling in regulating of Rad51 turnover and cytotoxic effects of topoisomerase II inhibitor, doxorubicin (Dox) in soft tissue sarcomas (STS) and gastrointestinal stromal tumors (GIST) in vitro. Blocking of AKT signaling (MK-2206) enhanced cytotoxic and pro-apoptotic effects of Dox in vast majority of STS and GIST cell lines. The phosphorylated form of Akt co-immunoprecipitates with Rad51 after Dox-induced DNA damage, whereas Akt inhibition interrupts this interaction and decreases Rad51 protein level by enhancing protein instability via proteasome-dependent degradation. Inhibition of Akt signaling in Dox-treated cells was associated with the increased number of γ-H2AX-positive cells, decrease of Rad51 foci formation and its colocalization with γ-H2AX foci, thereby revealing unsuccessful DDR events. This was also in consistency with an increase of tail moment (TM) and olive tail moment (OTM) in Dox-treated GIST and STS cells cultured in presence of Akt inhibitor after Dox washout. Altogether, our data illustrates that inhibition of AKT signaling is STS and GIST might potentiate the cytotoxic effect of topoisomerase II inhibitors via attenuating the homology-mediated DNA repair.
| S-EPMC7700672 | biostudies-literature
Project description:Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas.
| S-EPMC4344612 | biostudies-literature
Project description:The National Cancer Data Base (NCDB) of the American College of Surgeons gather demographic and survival data on ~70% of cancers in the USA. We wanted to investigate the demographic and survivorship data on this potentially more representative cohort of patients with soft tissue sarcomas. We selected 34 of the most commonly encountered soft tissue sarcomas reported to the NCDB, provided that each entity contained a minimum of 50 cases. This report summarizes the demographic and survivorship data on 63,714 patients with these 34 histologically distinct soft tissue sarcomas reported to the NCDB from 1998 to 2010. The overall survivorships of these sarcomas were near the lower limits of many prior reports due to the all-inclusive, minimally biased inclusion criteria. The overall best prognosis was Dermatofibrosarcoma NOS (not otherwise specified). (5-year survivorship 92%). The worst prognosis was Dedifferentiated Chondrosarcoma (5-year survivorship 19%). New observations included Biphasic Synovial Sarcoma demonstrating a better 5-year survivorship (65%) compared to spindle-cell synovial sarcoma (56%, P < 0.031) and Synovial Sarcoma, NOS (52%, P < 0.001). The demographic and 2- and 5-year survivorship data for all 34 soft tissue sarcomas are presented herein. This extent of demographic and survival data in soft tissue sarcomas is unprecedented. Because of the large number of cases and the inclusive nature of the NCDB, without restriction to certain stages, categories, or treatments, it is less subject to selection bias. Therefore, these data are thought to be more reflective of the true overall prognosis given the current management of sarcoma across the NCDB contributing sites.
| S-EPMC4302691 | biostudies-literature
Project description:Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a 'cold', non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.
| S-EPMC10052453 | biostudies-literature
Project description:The heterogeneity that soft tissue sarcomas (STS) exhibit in their clinical behavior, even within histological subtypes, complicates patient care. Histological appearance is determined by gene expression. Morphologic features are generally good predictors of biologic behavior, however, metastatic propensity, tumor growth, and response to chemotherapy may be determined by gene expression patterns that do not correlate well with morphology. One approach to identify heterogeneity is to search for genetic markers that correlate with differences in tumor behavior. Alternatively, subsets may be identified based on gene expression patterns alone, independent of knowledge of clinical outcome. We have reported gene expression patterns that distinguish two subgroups of clear cell renal carcinoma (ccRCC), and other gene expression patterns that distinguish heterogeneity of serous ovarian carcinoma (OVCA) and aggressive fibromatosis (AF). In this study, gene expression in 53 samples of STS and AF [including 16 malignant fibrous histiocytoma (MFH), 9 leiomyosarcoma, 12 liposarcoma, 4 synovial sarcoma, and 12 samples of AF] was determined at Gene Logic Inc. (Gaithersburg, MD) using Affymetrix GeneChip U_133 arrays containing approximately 40,000 genes/ESTs. Gene expression analysis was performed with the Gene Logic Genesis Enterprise System Software and Expressionist software. Hierarchical clustering of the STS using our three previously reported gene sets, each generated subgroups within the STS that for some subtypes correlated with histology, and also suggested the existence of subsets of MFH. All three gene sets also recognized the same two subsets of the fibromatosis samples that we had found in our earlier study of AF. These results suggest that these subgroups may have biological significance, and that these gene sets may be useful for sub-classification of STS. In addition, several genes that are targets of some anti-tumor drugs were found to be differentially expressed in particular subsets of STS.
| S-EPMC2412854 | biostudies-literature
Project description:Soft tissue sarcomas are rare neoplasms, with approximately 9000 new cases in the USA every year. Unfortunately, during the past two decades, there has been little progress in the treatment of metastatic soft tissue sarcomas beyond the standard approaches of surgery, chemotherapy and radiation. Immunotherapy is a modality complementary to conventional therapy. It is appealing because functional antitumor activity could affect both local-regional and systemic disease, and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies that are being developed, including several tumor vaccine, antigen vaccine and dendritic cell vaccine strategies.
| S-EPMC4501768 | biostudies-literature
Project description:Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma (STS). Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors, preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways. Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma, pazopanib was investigated in STS. A landmark phase III randomized study demonstrated improved progression-free survival with pazopanib compared to that with placebo in pretreated patients with STS of various subtypes. The efficacy of pazopanib in specific STS subtypes has been further described in real-world-based case series in both mixed and subtype-specific STS cohorts. At present, there are no clinically validated predictive biomarkers for use in selecting patients with advanced STS for pazopanib therapy, limiting the clinical effectiveness and cost-effectiveness of the drug. In this review, we summarize the preclinical and clinical data for pazopanib, outline the evidence base for its effect in STS and explore reported studies that have investigated putative biomarkers.
| S-EPMC6522548 | biostudies-literature