scholarly journals Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3044
Author(s):  
Serena Pillozzi ◽  
Andrea Bernini ◽  
Ilaria Palchetti ◽  
Olivia Crociani ◽  
Lorenzo Antonuzzo ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Predictive Biomarkers ◽  
Cellular Level ◽  
Comprehensive Overview ◽  
Novel Treatments ◽  
Patients At Risk ◽  
Prognostic Stratification ◽  
Biomarker Research ◽  
Metabolic Biomarkers

Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.

scholarly journals Musculoskeletal Soft-Tissue Sarcoma: Quality Assessment of Initial MRI Reports Shows Frequent Deviation from ESSR Guidelines

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 695
Author(s):  
Sebastian Weiss ◽  
Alexander Korthaus ◽  
Nora Baumann ◽  
Jin Yamamura ◽  
Alexander S. Spiro ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Quality Criteria ◽  
Final Diagnosis ◽  
Tissue Mass ◽  
Musculoskeletal Radiology ◽  
Radiology Reports ◽  
Patients At Risk ◽  
Magnetic Resonance Imaging Mri ◽  
The Masses

Soft-tissue sarcomas (STS) are a rare subtype of soft-tissue mass and are frequently misinterpreted as benign lesions. Magnetic resonance imaging (MRI) is the primary recommended type of diagnostics. To assess the quality of primary radiology reports, we investigated whether recommended MRI report elements were included in compliance with European Society of Musculoskeletal Radiology (ESSR) guidelines. A total of 1107 patients were evaluated retrospectively, and 126 radiological reports on patients with malignant STS were assessed for ESSR quality criteria. One or more required sequences or planes were missing in 67% of the reports. In all 126 cases, the report recognized the mass as anomalous (100%). Sixty-eight percent of the reports mentioned signs of malignancy. The majority of reports (n = 109, 87%) articulated a suspected diagnosis, 32 of which showed a mismatch with the final diagnosis (25%). Thirty-two percent of the reports had a misinterpretation of the masses as benign. Benign misinterpretations were more common in masses smaller than 5 cm (65% vs. 27%). Thirty percent of the reports suggested tissue biopsy and 6% recommended referral to a sarcoma center. MRI reports showed frequent deviations from ESSR guidelines, and protocol guidelines were not routinely met. Deviations from standard protocol and reporting guidelines could put patients at risk for inadequate therapy.

scholarly journals Liquid Biopsy in Hepatocellular Carcinoma: Where Are We Now?

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2274
Author(s):  
Filippo Pelizzaro ◽  
Romilda Cardin ◽  
Barbara Penzo ◽  
Elisa Pinto ◽  
Alessandro Vitale ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Predictive Biomarkers ◽  
Invasive Procedure ◽  
Therapeutic Monitoring ◽  
Comprehensive Overview ◽  
Improve Patient Survival ◽  
Prognostic Tests ◽  
Prognostic Stratification ◽  
New Biomarkers

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Diagnostic, prognostic, and predictive biomarkers are urgently needed in order to improve patient survival. Indeed, the most widely used biomarkers, such as alpha-fetoprotein (AFP), have limited accuracy as both diagnostic and prognostic tests. Liver biopsy provides an insight on the biology of the tumor, but it is an invasive procedure, not routinely used, and not representative of the whole neoplasia due to the demonstrated intra-tumoral heterogeneity. In recent years, liquid biopsy, defined as the molecular analysis of cancer by-products, released by the tumor in the bloodstream, emerged as an appealing source of new biomarkers. Several studies focused on evaluating extracellular vesicles, circulating tumor cells, cell-free DNA and non-coding RNA as novel reliable biomarkers. In this review, we aimed to provide a comprehensive overview on the most relevant available evidence on novel circulating biomarkers for early diagnosis, prognostic stratification, and therapeutic monitoring. Liquid biopsy seems to be a very promising instrument and, in the near future, some of these new non-invasive tools will probably change the clinical management of HCC patients.

A randomized phase II study of durvalumab and tremelimumab compared to doxorubicin in patients with advanced or metastatic soft tissue sarcoma (MEDISARC, AIO-STS 0415).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS11075-TPS11075
Author(s):  
Viktor Grünwald ◽  
Sebastian Bauer ◽  
Barbara Hermes ◽  
Philipp Ivanyi ◽  
Lars H Lindner ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Soft Tissue ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Soft Tissue Sarcomas ◽  
Predictive Biomarkers ◽  
Ecog Performance Status ◽  
Curative Intent

TPS11075 Background: Soft tissue sarcomas (STS) are rare tumors and exhibit substantial histological diversity. Efficacious targeted 1st line treatment for advanced or metastatic STS is not available, and the standard therapy has been anthracycline-based for decades. This strategy shows poor efficacy, as demonstrated by a median Overall Survival (OS) of 12-20 months. Several STS subtypes, however, have been shown to express PD-L1, and immune checkpoint inhibitors (ICI) have demonstrated principle anti-tumor activity in pretreated STS. Our ongoing clinical trial tests the activity and safety of ICI combination therapy in the first-line setting. We hypothesize that the dual checkpoint blockade with Durvalumab (PD-L1) and Tremelimumab (CTLA-4) improves overall survival in STS when compared to the standard of care doxorubicin. Methods: MEDISARC is a multi-center phase II trial that is enrolling adult treatment-naïve patients with histologically confirmed STS of intermediate or high grade (FNCLCC grade 2 or 3) not amenable to surgery with curative intent and ECOG performance status 0-2. Chemosensitive histologic STS are eligible. 100 patients will be randomized 1:1, stratified by ECOG status (0 vs. 1/2). Patients in the experimental arm are treated with fixed doses of durvalumab (1.5 g Q4W) and tremelimumab (75 mg Q4W for 3 cycles, then Q12W) until Progressive Disease (PD) or for a maximum of 12 months. Doxorubicin treatment in the standard arm is at 75 mg/m2 Q3W and limited to 6 cycles. OS is the primary endpoint. Secondary endpoints include 2-year OS rate, PFS, ORR according to conventional and modified RECIST 1.1, safety and tolerability and health-related quality of life (EORTC QLQ-C30). OS analysis may be performed when the required number of events (E=70) has been observed. All randomized and treated subjects will be included in the efficacy and safety analysis. The accompanying translational research aims to identify prognostic and predictive biomarkers in blood and tumor tissue. Enrollment of patients started in April 2018 and is ongoing. As of February 2019, 32 patients have been enrolled. The study is sponsored by AIO-Studien-gGmbH, Berlin, Germany. Clinical trial information: 2016-004750-15.

scholarly journals CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1128 ◽  
Author(s):  
David S. Moura ◽  
Paloma Sanchez-Bustos ◽  
Antonio Fernandez-Serra ◽  
María Lopez-Alvarez ◽  
José L. Mondaza-Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Soft Tissue ◽  
Cell Lines ◽  
Predictive Factors ◽  
Excision Repair ◽  
Soft Tissue Sarcomas ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Expression Levels ◽  
Protein Levels

A translational study was designed to analyze the expression of nucleotide excision repair (NER) and homologous recombination (HR) genes as potential predictive biomarkers for trabectedin in soft-tissue sarcoma (STS). This study is part of a randomized phase II trial comparing trabectedin plus doxorubicin versus doxorubicin in advanced STS. Gene expression levels were evaluated by qRT-PCR, while CUL4A protein levels were quantified by immunohistochemistry. Expression levels were correlated with patients’ progression-free survival (PFS) and overall survival (OS). Gene expression was also evaluated in cell lines and correlated with trabectedin sensitivity. In doxorubicin arm and in the whole series, which includes samples from both arms, no significant differences in terms of PFS were observed amongst the analyzed genes. In the group treated with trabectedin plus doxorubicin, the median of PFS was significantly longer in cases with CUL4A, ERCC1, or ERCC5 overexpression, while BRCA1 expression did not correlated with PFS. Gene expression had no prognostic influence in OS. CUL4A protein levels correlated with worse PFS in doxorubicin arm and in the whole series. In cell lines, only overexpression of ERCC1 was significantly correlated with trabectedin sensitivity. In conclusion, CUL4A, ERCC5, and mainly ERCC1 acted as predictive factors for trabectedin efficacy in advanced STS.

scholarly journals Genetic Characterization, Current Model Systems and Prognostic Stratification in PAX Fusion-Negative vs. PAX Fusion-Positive Rhabdomyosarcoma

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1500
Author(s):  
Carina A. Dehner ◽  
Amy E. Armstrong ◽  
Marielle Yohe ◽  
Jack F. Shern ◽  
Angela C. Hirbe
Keyword(s):  
Soft Tissue ◽  
Risk Stratification ◽  
Genetic Characterization ◽  
Current Model ◽  
Soft Tissue Sarcomas ◽  
Model Systems ◽  
Genetic Pathways ◽  
Genetic Abnormalities ◽  
Prognostic Stratification ◽  
Molecular Landscape

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and accounts for approximately 2% of soft tissue sarcomas in adults. It is subcategorized into distinct subtypes based on histological features and fusion status (PAX-FOXO1/VGLL2/NCOA2). Despite advances in our understanding of the pathobiological and molecular landscape of RMS, the prognosis of these tumors has not significantly improved in recent years. Developing a better understanding of genetic abnormalities and risk stratification beyond the fusion status are crucial to developing better therapeutic strategies. Herein, we aim to highlight the genetic pathways/abnormalities involved, specifically in fusion-negative RMS, assess the currently available model systems to study RMS pathogenesis, and discuss available prognostic factors as well as their importance for risk stratification to achieve optimal therapeutic management.

scholarly journals Soft Tissue Sarcomas - Series of Cases in One Surgical Department

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 50
Author(s):  
R.V. Costea ◽  
N. Zărnescu ◽  
A. Chirca ◽  
O. Rusu ◽  
S. Neagu
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Soft Tissue Sarcomas ◽  
Operative Therapy ◽  
Predictive Biomarkers ◽  
Tumor Type ◽  
Total Excision ◽  
Surgical Department ◽  
Safety Margins

Abstract Introduction. Soft tissue sarcomas (STS) are a heterogeneous group of tumors with over 80 different subtypes that account for approximately 1-2% of adult malignancies. Primary sarcomas arise from a variety of soft tissues and bone, and include fibrous connective, fat, and smooth, or striated muscle, vascular, peripheral neural and visceral tissue. With difficulties in establishing cell origin and pathogenesis, this condition lacks an effective and durable therapy with no predictive biomarkers and rapid diagnosis. Materials and methods. We reviewed the cases of 21 patients treated in our clinic for soft tissue sarcoma over a 20-year period (1999-2018). We extracted the following information from each patient’s medical record: disease status at presentation, histological diagnosis, American Joint Committee on Cancer staging, surgical procedure, oncological outcome, length of hospitalization, and follow-up information. Results. All 21 patients (14 males and 7 females, aged between 19 and 88 years) underwent surgery and total excision with safety margins was performed with histopathological confirmation stating the tumor type and subtype. Some samples required immunohistochemistry for subtype differentiation. Chondrosarcoma and myosarcoma were the most common (5 patients). 8 patients presented local recurrence and metastatic disease with 6 cases receiving adjuvant chemotherapy. Only one patient presented for the 5-year follow-up. Conclusions. STS are a rare group of tumors with poor outcome with surgical treatment being represented by total excision. We chose to present our clinic’s experience to highlight the need for post-operative therapy advancements and to raise awareness on the difficulties in managing these cases.

Sign in / Sign up

Export Citation Format

Share Document