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Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis...
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Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (10 April 2022) | Viewed by 40822

Special Issue Editor

Prof. Dr. Justus P. Beier

E-Mail Website
Guest Editor
Department of Plastic Surgery, Hand Surgery - Burn Center, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany
Interests: soft tissue sarcoma treatment; reconstructive surgery; tissue engineering of musculoskeletal tissues

Special Issue Information

Dear Colleagues,

Despite being relatively rare tumors, soft and hard tissue sarcomas contribute to a significant number of patients needing treatment. Diagnostic and treatment concepts for soft and hard tissue sarcomas have advanced in recent years. In this review, established and recently developed diagnostic tools, ranging from new immunohistochemical markers and genetic profiling to liquid biopsies and mRNA-based diagnostics in sarcomas, will be elucidated.

Surgery is the first line of treatment in many sarcoma cases, comprising orthopedic surgery, plastic surgery, as well as general and visceral surgery, often in an interdisciplinary approach. Hence, current concepts for surgical treatment of soft and hard tissue sarcomas of the trunk and extremities, as well as reconstructive options, will be in the focus of the surgical contributions to this Special Issue. We also provide a contribution about the current status of adjuvant chemotherapy, including new biologicals, for the curative and palliative treatment of soft and hard tissue sarcomas. Finally, new innovative approaches for sarcoma disease modelling in vitro and in vivo are highlighted, and future perspectives for experimental models will be outlined.  

In summary, the aim of this Special Issue is to highlight recent studies on sarcoma diagnostics, medical and surgical sarcoma treatment, including reconstructive surgery, and future perspectives based on experimental models for sarcoma research.

Prof. Dr. Justus P. Beier
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • soft tissue sarcoma
  • hard tissue sarcoma
  • imaging in sarcoma diagnostics
  • liquid biopsy
  • sarcoma treatment
  • reconstructive surgery

Published Papers (14 papers)

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Research

Jump to: Review, Other

11 pages, 1277 KiB  
Article
Sensitivity, Specificity, and Predictive Values of Tru-Cut® Biopsy in Grading Primary Localized Myxoid Liposarcomas of the Extremities
by Giuseppe Bianchi, Roberta Laranga, Paolo Spinnato, Federico Ostetto, Elisa Bubbico, Alberto Righi and Davide Maria Donati
Cancers 2023, 15(5), 1391; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051391 - 22 Feb 2023
Cited by 2 | Viewed by 1138
Abstract
(1) Background: Histological diagnosis and tumor grading are major prognostic and predictive factors in soft tissue sarcomas (STS), as they dictate the treatment strategies with a direct impact on patient survival. This study aims to investigate the grading accuracy, sensitivity, and specificity of [...] Read more.
(1) Background: Histological diagnosis and tumor grading are major prognostic and predictive factors in soft tissue sarcomas (STS), as they dictate the treatment strategies with a direct impact on patient survival. This study aims to investigate the grading accuracy, sensitivity, and specificity of Tru-Cut® biopsy (TCB) in primary localized myxoid liposarcomas (MLs) of the extremities and its impact on patient prognosis. (2) Methods: Patients with ML undergoing TCB and a subsequent tumor resection between 2007 and 2021 were evaluated. Concordance between the preoperative assessment and definitive histology was calculated with a weighted Cohen’s kappa coefficient. Sensitivity, specificity, and diagnostic accuracy were calculated. (3) Results: Of 144 biopsies, the histological grade concordance rate was 63% (Kappa 0.2819). Neoadjuvant chemotherapy and/or radiotherapy impacted concordance with a downgrading effect in high-grade tumors. Among forty patients not treated in neoadjuvant settings, the sensitivity of TCB was 57%, the specificity was 100%, and the overall predictive values of positive and negative TCB were 100% and 50%, respectively. Misdiagnosis did not impact overall survival. (4) Conclusions: TCB may underestimate ML grading due to tumor heterogeneity. Neoadjuvant ChT and/or radiotherapy are associated with pathological downgrading; however, discordance in diagnosis does not modify patient prognosis because systemic treatment decision-making also includes other variables. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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15 pages, 1256 KiB  
Article
The Therapeutic Role of Plastic and Reconstructive Surgery in the Interdisciplinary Treatment of Soft-Tissue Sarcomas in Germany—Cross-Sectional Results of a Prospective Nationwide Observational Study (PROSa)
by Benjamin Thomas, Amir K. Bigdeli, Steffen Nolte, Emre Gazyakan, Leila Harhaus, Oliver Bischel, Burkhard Lehner, Gerlinde Egerer, Gunhild Mechtersheimer, Peter Hohenberger, Raymund E. Horch, Dimosthenis Andreou, Jochen Schmitt, Markus K. Schuler, Martin Eichler and Ulrich Kneser
Cancers 2022, 14(17), 4312; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174312 - 02 Sep 2022
Cited by 2 | Viewed by 1324
Abstract
Although the involvement of plastic surgery has been deemed important in the treatment of sarcoma patients to avoid oncological compromises and ameliorate patient outcomes, it is not ubiquitously available. The accessibility of defect reconstruction and its therapeutic impact on sarcoma care is the [...] Read more.
Although the involvement of plastic surgery has been deemed important in the treatment of sarcoma patients to avoid oncological compromises and ameliorate patient outcomes, it is not ubiquitously available. The accessibility of defect reconstruction and its therapeutic impact on sarcoma care is the subject of this analysis. Cross-sectional data from 1309 sarcoma patients were collected electronically at 39 German study centers from 2017 to 2019. A total of 621 patients with surgical treatment for non-visceral soft-tissue sarcomas were included. The associated factors were analyzed exploratively using multifactorial logistic regression to identify independent predictors of successful defect reconstruction, as well Chi-squared and Cochran–Mantel–Haenszel tests to evaluate subgroups, including limb-salvage rates in extremity cases. A total of 76 patients received reconstructive surgery, including 52 local/pedicled versus 24 free flaps. Sarcomas with positive margins upon first resection (OR = 2.3, 95%CI = 1.2–4.4) that were excised at centers with lower degrees of specialization (OR = 2.2, 95%CI = 1.2–4.2) were independently associated with the need for post-oncological defect coverage. In this context, the inhouse availability of plastic surgery (OR = 3.0, 95%CI = 1.6–5.5) was the strongest independent predictor for successful flap-based reconstruction, which in turn was associated with significantly higher limb-salvage rates (OR = 1.4, 95%CI = 1.0–2.1) in cases of extremity sarcomas (n = 366, 59%). In conclusion, consistent referral to specialized interdisciplinary sarcoma centers significantly ameliorates patient outcomes by achieving higher rates of complete resections and offering unrestricted access to plastic surgery. The latter in particular proved indispensable for limb salvage through flap-based defect reconstruction after sarcoma resection. In fact, although there remains a scarcity of readily available reconstructive surgery services within the current sarcoma treatment system in Germany, plastic and reconstructive flap transfer was associated with significantly increased limb-salvage rates in our cohort. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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10 pages, 2996 KiB  
Article
Oncological Safety and Recurrence in the Surgical Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma of the Scalp
by Johannes Zeller, Jurij Kiefer, David Braig, Oscar Winninger, Daniel Kraus, Salome Hagelstein and Steffen U. Eisenhardt
Cancers 2022, 14(12), 2869; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14122869 - 10 Jun 2022
Cited by 2 | Viewed by 2710
Abstract
Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic [...] Read more.
Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic features, they significantly differ in prognosis. Here we present a retrospective single-center chart review analyzing the outcomes of patients treated for dermal sarcoma. The radicality of the tumor-resection extent and soft-tissue reconstructive options were assessed. Patients between January 2010 and August 2021 were included. We recorded resection margins, tumor recurrence, overall survival, number of operations until complete tumor resection, and reconstructive procedures; any complications were recorded. Furthermore, we analyzed a subgroup of patients with satellite metastases. A total of 32 patients met the inclusion criteria (30 male, 2 female, median age of 77.5 years (interquartile range (IQR) 74–81)). Histopathology revealed AFX in 14 patients and PDS in 18 patients. Margin-free resection was achieved in 31 cases, and 27 patients were remission free over the reported period. The local recurrence rate was 5, and distant metastasis was detected in four cases. Of all the PDS cases, nine presented with satellite metastasis. No AFX had satellite metastases. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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18 pages, 2140 KiB  
Article
Telomere as a Therapeutic Target in Dedifferentiated Liposarcoma
by Irene Alessandrini, Stefano Percio, Eisa Naghshineh, Valentina Zuco, Silvia Stacchiotti, Alessandro Gronchi, Sandro Pasquali, Nadia Zaffaroni and Marco Folini
Cancers 2022, 14(11), 2624; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112624 - 25 May 2022
Cited by 1 | Viewed by 2031
Abstract
Background: Well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS) accounts for ~60% of retroperitoneal sarcomas. WDLPS and DDLPS divergently evolve from a common precursor and are both marked by the amplification of the 12q13–q15 region, leading to the abnormal expression of MDM2, CDK4, and [...] Read more.
Background: Well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS) accounts for ~60% of retroperitoneal sarcomas. WDLPS and DDLPS divergently evolve from a common precursor and are both marked by the amplification of the 12q13–q15 region, leading to the abnormal expression of MDM2, CDK4, and HMGA2 genes. DDLPS is a non-lipogenic disease associated with aggressive clinical behavior. Patients have limited therapeutic options, especially for advanced disease, and their outcome remains largely unsatisfactory. This evidence underlines the need for identifying and validating DDLPS-specific actionable targets to design novel biology-driven therapies. Methods: Following gene expression profiling of DDLPS clinical specimens, we observed the up-regulation of “telomere maintenance” (TMM) pathways in paired DD and WD components of DDLPS. Considering the relevance of TMM for LPS onset and progression, the activity of a telomeric G-quadruplex binder (RHPS4) was assessed in DDLPS patient-derived cell lines. Results: Equitoxic concentrations of RHPS4 in DDLPS cells altered telomeric c-circle levels, induced DNA damage, and resulted in the accumulation of γ-H2AX-stained micronuclei. This evidence was paralleled by an RHPS4-mediated reduction of in vitro cell migration and induction of apoptosis/autophagy. Conclusions: Our findings support telomere as an intriguing therapeutic target in DDLPS and suggest G-quadruplex binders as innovative therapeutic agents. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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Graphical abstract

14 pages, 2914 KiB  
Article
Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas
by Anja E. Eisenhardt, Zacharias Brugger, Ute Lausch, Jurij Kiefer, Johannes Zeller, Alexander Runkel, Adrian Schmid, Peter Bronsert, Julius Wehrle, Andreas Leithner, Bernadette Liegl-Atzwanger, Riccardo E. Giunta, Steffen U. Eisenhardt and David Braig
Cancers 2022, 14(9), 2078; https://doi.org/10.3390/cancers14092078 - 21 Apr 2022
Cited by 6 | Viewed by 1689
Abstract
Background: Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which [...] Read more.
Background: Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection. Methods: We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses SS18 (SYT) in chromosome 18 to SSX1 or SSX2 in chromosome x, and recurrent point mutations. In addition, patient-specific panels were designed from tumor exome sequencing. Both approaches were used to quantify ctDNA in patients’ plasma. Results: The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples (n = 11) from one patient collected over 3 years, with a patient-specific panel based on tumor exome sequencing, correlated with the clinical course, response to treatment and tumor volume. Conclusions: Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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12 pages, 2070 KiB  
Article
A Highly Reliable Convolutional Neural Network Based Soft Tissue Sarcoma Metastasis Detection from Chest X-ray Images: A Retrospective Cohort Study
by Christoph Wallner, Mansoor Alam, Marius Drysch, Johannes Maximilian Wagner, Alexander Sogorski, Mehran Dadras, Maxi von Glinski, Felix Reinkemeier, Mustafa Becerikli, Christoph Heute, Volkmar Nicolas, Marcus Lehnhardt and Björn Behr
Cancers 2021, 13(19), 4961; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13194961 - 01 Oct 2021
Cited by 3 | Viewed by 1991
Abstract
Introduction: soft tissue sarcomas are a subset of malignant tumors that are relatively rare and make up 1% of all malignant tumors in adulthood. Due to the rarity of these tumors, there are significant differences in quality in the diagnosis and treatment of [...] Read more.
Introduction: soft tissue sarcomas are a subset of malignant tumors that are relatively rare and make up 1% of all malignant tumors in adulthood. Due to the rarity of these tumors, there are significant differences in quality in the diagnosis and treatment of these tumors. One paramount aspect is the diagnosis of hematogenous metastases in the lungs. Guidelines recommend routine lung imaging by means of X-rays. With the ever advancing AI-based diagnostic support, there has so far been no implementation for sarcomas. The aim of the study was to utilize AI to obtain analyzes regarding metastasis on lung X-rays in the most possible sensitive and specific manner in sarcoma patients. Methods: a Python script was created and trained using a set of lung X-rays with sarcoma metastases from a high-volume German-speaking sarcoma center. 26 patients with lung metastasis were included. For all patients chest X-ray with corresponding lung CT scans, and histological biopsies were available. The number of trainable images were expanded to 600. In order to evaluate the biological sensitivity and specificity, the script was tested on lung X-rays with a lung CT as control. Results: in this study we present a new type of convolutional neural network-based system with a precision of 71.2%, specificity of 90.5%, sensitivity of 94%, recall of 94% and accuracy of 91.2%. A good detection of even small findings was determined. Discussion: the created script establishes the option to check lung X-rays for metastases at a safe level, especially given this rare tumor entity. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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Review

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29 pages, 1382 KiB  
Review
Proteasome Inhibitors and Their Potential Applicability in Osteosarcoma Treatment
by Cassidy M. Van Stiphout, Anita K. Luu and Alicia M. Viloria-Petit
Cancers 2022, 14(19), 4544; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194544 - 20 Sep 2022
Cited by 8 | Viewed by 2253
Abstract
Osteosarcoma (OS) is the most common type of bone cancer, with ~30% of patients developing secondary/metastatic tumors. The molecular complexity of tumor metastasis and the lack of effective therapies for OS has cultivated interest in exploiting the proteasome as a molecular target for [...] Read more.
Osteosarcoma (OS) is the most common type of bone cancer, with ~30% of patients developing secondary/metastatic tumors. The molecular complexity of tumor metastasis and the lack of effective therapies for OS has cultivated interest in exploiting the proteasome as a molecular target for anti-cancer therapy. As our understanding towards the behavior of malignant cells expands, it is evident that cancerous cells display a greater reliance on the proteasome to maintain homeostasis and sustain efficient biological activities. This led to the development and approval of first- and second-generation proteasome inhibitors (PIs), which have improved outcomes for patients with multiple myeloma and mantle cell lymphoma. Researchers have since postulated the therapeutic potential of PIs for the treatment of OS. As such, this review aims to summarize the biological effects and latest findings from clinical trials investigating PI-based treatments for OS. Integrating PIs into current treatment regimens may better outcomes for patients diagnosed with OS. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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20 pages, 621 KiB  
Review
The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma
by Johannes Tobias Thiel, Adrien Daigeler, Jonas Kolbenschlag, Katarzyna Rachunek and Sebastian Hoffmann
Cancers 2022, 14(14), 3380; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14143380 - 12 Jul 2022
Cited by 7 | Viewed by 2563
Abstract
Soft tissue sarcomas (STSs) are tumors that are challenging to treat due to their pathologic and molecular heterogeneity and their tumor biology that is not yet fully understood. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong [...] Read more.
Soft tissue sarcomas (STSs) are tumors that are challenging to treat due to their pathologic and molecular heterogeneity and their tumor biology that is not yet fully understood. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong driver of sarcogenesis. CDKs are enzyme forms that play a crucial role in cell-cycle control and transcription. They belong to the protein kinases group and to the serine/threonine kinases subgroup. Recently identified CDK/cyclin complexes and established CDK/cyclin complexes that regulate the cell cycle are involved in the regulation of gene expression through phosphorylation of critical components of transcription and pre-mRNA processing mechanisms. The current and continually growing body of data shows that CDKs play a decisive role in tumor development and are involved in the proliferation and growth of sarcoma cells. Since the abnormal expression or activation of large numbers of CDKs is considered to be characteristic of cancer development and progression, dysregulation of the CDK signaling pathways occurs in many subtypes of STSs. This review discusses how reversal and regulation can be achieved with new therapeutics and summarizes the current evidence from studies regarding CDK modulation for STS treatment. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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21 pages, 2578 KiB  
Review
Surgical Treatment of Bone Sarcoma
by Felix Bläsius, Heide Delbrück, Frank Hildebrand and Ulf Krister Hofmann
Cancers 2022, 14(11), 2694; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112694 - 29 May 2022
Cited by 17 | Viewed by 8084
Abstract
Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic [...] Read more.
Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structures. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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15 pages, 327 KiB  
Review
The Molecular Biology of Soft Tissue Sarcomas: Current Knowledge and Future Perspectives
by Julien Vibert and Sarah Watson
Cancers 2022, 14(10), 2548; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102548 - 22 May 2022
Cited by 6 | Viewed by 2537
Abstract
Soft tissue sarcomas are malignant tumors of mesenchymal origin, encompassing a large spectrum of entities that were historically classified according to their histological characteristics. Over the last decades, molecular biology has allowed a better characterization of these tumors, leading to the incorporation of [...] Read more.
Soft tissue sarcomas are malignant tumors of mesenchymal origin, encompassing a large spectrum of entities that were historically classified according to their histological characteristics. Over the last decades, molecular biology has allowed a better characterization of these tumors, leading to the incorporation of multiple molecular features in the latest classification of sarcomas as well as to molecularly-guided therapeutic strategies. This review discusses the main uses of molecular biology in current practice for the diagnosis and treatment of soft tissue sarcomas, in addition to perspectives for this rapidly evolving field of research. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
17 pages, 1368 KiB  
Review
Pediatric Sarcomas: The Next Generation of Molecular Studies
by Petros Giannikopoulos and David M. Parham
Cancers 2022, 14(10), 2515; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102515 - 20 May 2022
Viewed by 2743
Abstract
Pediatric sarcomas constitute one of the largest groups of childhood cancers, following hematopoietic, neural, and renal lesions. Partly because of their diversity, they continue to offer challenges in diagnosis and treatment. In spite of the diagnostic, nosologic, and therapeutic gains made with genetic [...] Read more.
Pediatric sarcomas constitute one of the largest groups of childhood cancers, following hematopoietic, neural, and renal lesions. Partly because of their diversity, they continue to offer challenges in diagnosis and treatment. In spite of the diagnostic, nosologic, and therapeutic gains made with genetic technology, newer means for investigation are needed. This article reviews emerging technology being used to study human neoplasia and how these methods might be applicable to pediatric sarcomas. Methods reviewed include single cell RNA sequencing (scRNAseq), spatial multi-omics, high-throughput functional genomics, and clustered regularly interspersed short palindromic sequence-Cas9 (CRISPR-Cas9) technology. In spite of these advances, the field continues to be challenged by a dearth of properly annotated materials, particularly from recurrences and metastases and pre- and post-treatment samples. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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25 pages, 401 KiB  
Review
Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions
by Klaudia Żak, Bartłomiej Zaremba, Alicja Rajtak, Jan Kotarski, Frédéric Amant and Marcin Bobiński
Cancers 2022, 14(8), 1966; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081966 - 13 Apr 2022
Cited by 15 | Viewed by 2624
Abstract
The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to [...] Read more.
The distinguishing of uterine leiomyosarcomas (ULMS) and uterine leiomyomas (ULM) before the operation and histopathological evaluation of tissue is one of the current challenges for clinicians and researchers. Recently, a few new and innovative methods have been developed. However, researchers are trying to create different scales analyzing available parameters and to combine them with imaging methods with the aim of ULMs and ULM preoperative differentiation ULMs and ULM. Moreover, it has been observed that the technology, meaning machine learning models and artificial intelligence (AI), is entering the world of medicine, including gynecology. Therefore, we can predict the diagnosis not only through symptoms, laboratory tests or imaging methods, but also, we can base it on AI. What is the best option to differentiate ULM and ULMS preoperatively? In our review, we focus on the possible methods to diagnose uterine lesions effectively, including clinical signs and symptoms, laboratory tests, imaging methods, molecular aspects, available scales, and AI. In addition, considering costs and availability, we list the most promising methods to be implemented and investigated on a larger scale. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
14 pages, 2005 KiB  
Review
A Multidisciplinary Approach to Complex Dermal Sarcomas Ensures an Optimal Clinical Outcome
by Hannah Trøstrup, Amir K. Bigdeli, Christina Krogerus, Ulrich Kneser, Grethe Schmidt and Volker J. Schmidt
Cancers 2022, 14(7), 1693; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071693 - 26 Mar 2022
Cited by 4 | Viewed by 4395
Abstract
Primary dermal sarcomas (PDS) belong to a highly clinically, genetically and pathologically heterogeneous group of rare malignant mesenchymal tumours primarily involving the dermis or the subcutaneous tissue. The tumours are classified according to the mesenchymal tissue from which they originate: dermal connective tissue, [...] Read more.
Primary dermal sarcomas (PDS) belong to a highly clinically, genetically and pathologically heterogeneous group of rare malignant mesenchymal tumours primarily involving the dermis or the subcutaneous tissue. The tumours are classified according to the mesenchymal tissue from which they originate: dermal connective tissue, smooth muscle or vessels. Clinically, PDS may mimic benign soft tissue lesions such as dermatofibromas, hypertrophic scarring, etc. This may cause substantial diagnostic delay. As a group, PDS most commonly comprises the following clinicopathological forms of dermal sarcomas: dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), dermal undifferentiated pleomorphic sarcoma (DUPS), leiomyosarcoma (LMS), and vascular sarcomas (Kaposi’s sarcoma, primary angiosarcoma, and radiation-induced angiosarcoma). This clinical entity has a broad spectrum regarding malignant potential; however, local aggressive behaviour in some forms causes surgical challenges. Preoperative, individualised surgical planning with complete free margins is pivotal along with a multidisciplinary approach and collaboration across highly specialised surgical and medical specialties. The present review gives a structured overview of the most common forms of dermal sarcomas including surgical recommendations and examples for advanced reconstructions as well as the current adjunctive medical treatment strategies. Optimal aesthetic and functional outcomes with low recurrence rates can be achieved by using a multidisciplinary approach to complex dermal sarcomas. In cases of extended local tumour invasion in dermal sarcomas, advanced reconstructive techniques can be applied, and the interdisciplinary microsurgeon should be an integral part of the sarcoma board. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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Other

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16 pages, 2125 KiB  
Systematic Review
Risk Factors for Occurrence and Relapse of Soft Tissue Sarcoma
by Pia Weskamp, Dominic Ufton, Marius Drysch, Johannes Maximilian Wagner, Mehran Dadras, Marcus Lehnhardt, Björn Behr and Christoph Wallner
Cancers 2022, 14(5), 1273; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051273 - 01 Mar 2022
Cited by 9 | Viewed by 2306
Abstract
The diagnosis and prognostic outcome of STS pose a therapeutic challenge in an interdisciplinary setting. The treatment protocols are still discussed controversially. This systematic meta-analysis aimed to determine prognostic factors leading to the development and recurrence of STS. Eligible studies that investigated potential [...] Read more.
The diagnosis and prognostic outcome of STS pose a therapeutic challenge in an interdisciplinary setting. The treatment protocols are still discussed controversially. This systematic meta-analysis aimed to determine prognostic factors leading to the development and recurrence of STS. Eligible studies that investigated potential risk factors such as smoking, genetic dispositions, toxins, chronic inflammation as well as prognostic relapse factors including radiation, chemotherapy and margins of resection were identified. Data from 24 studies published between 1993 and 2019 that comprised 6452 patients were pooled. A statistically significant effect developing STS was found in overall studies stating a causality between risk factors and the development of STS (p < 0.01). Although subgroup analysis did not meet statistical significances, it revealed a greater magnitude with smoking (p = 0.23), genetic predisposition (p = 0.13) chronic inflammation, (p = 0.20), and toxins (p = 0.14). Secondly, pooled analyses demonstrated a higher risk of relapse for margin of resection (p = 0.78), chemotherapy (p = 0.20) and radiation (p = 0.16); after 3 years of follow-up. Therefore, we were able to identify risk and relapse prognostic factors for STS, helping to diagnose and treat this low incidental cancer properly. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Sarcoma—Current and Future Concepts in Diagnosis and Treatment)
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