Soft Tissue Sarcoma: Imaging, Mechanisms and Therapy

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 10625

Special Issue Editors


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Guest Editor
Department of Surgical, Oncological, and Oral Sciences, Section of Medical Oncology, University of Palermo, Via Del Vespro 127, Palermo, Italy
Interests: soft tissue sarcomas; gastrointestinal stromal tumors; neuroendocrine tumors
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Guest Editor
Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University Hospital “Paolo Giaccone”, Via del Vespro 129, 90127 Palermo, Italy
Interests: abdominal imaging; emergency radiology; liver imaging; pancreatic imaging; radiomics
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Sarcoma Unit, Royal Marsden Hospital, 203 Fulham Rd, London SW3 6JJUK, United Kingdom
Interests: soft tissue sarcomas; gastrointestinal stromal tumors; translational research

Special Issue Information

Dear Colleagues, 

Soft tissue sarcomas are rare cancers and very heterogeneous neoplasms. For this reason, histological diagnosis is often very difficult, and the correct therapeutic approach is highly complex.

In localized disease, surgery is the standard treatment. Recently, neoadjuvant chemo-radiotherapy has been increasingly used in high-risk patients in an effort to reduce surgical morbidity and improve clinical outcomes. For this reason, imaging plays a crucial role in diagnosis and evaluation in response to treatment. Although response evaluation criteria in solid tumours (RECIST) is the most common imaging method to assess tumour response, Choi criteria and functional and molecular imaging (DWI, DCE-MRI and 18F-FDG-PET) seem to outperform it in the discrimination between responders and non-responders.

In recent years, several biological targets have been identified for new treatments, and this has changed the approach, especially in the second line of treatment.  In fact, the first-line treatment of soft tissue sarcomas is well standardized, but second-line treatment can vary depending on the histotype (histology-driven treatment) and biological features. Immunotherapy has reported disappointing results, showing some activity only against some particular histologies.

In this Special Issue, experts in this field will review current approaches to the management of patients with sarcomas, and will also focus on the imaging and molecular aspects of this heterogeneous group of neoplasms.

It is with great pleasure that we introduce you to the Cancers Special Issue on “Soft Tissue Sarcomas: Imaging, Biology and Therapy”. This Special Issue aims to focus on new imaging techniques, such as radiomics, alongside the biology and treatment of these neoplasms. Original research articles on these topics are welcome; reviews are also welcome if they clarify the more complex aspects of soft tissue sarcoma management.

We look forward to receiving your contributions.

Dr. Giuseppe Badalamenti
Dr. Roberto Cannella
Dr. Andrea Napolitano
Guest Editors

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

  • sarcomas
  • target therapy
  • immunotherapy
  • cancer biology
  • radiomics

Published Papers (4 papers)

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Research

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14 pages, 8375 KiB  
Article
Combination of Everolimus and Bortezomib Inhibits the Growth and Metastasis of Bone and Soft Tissue Sarcomas via JNK/p38/ERK MAPK and AKT Pathways
by Koichi Nakamura, Kunihiro Asanuma, Takayuki Okamoto, Takahiro Iino, Tomohito Hagi, Tomoki Nakamura and Akihiro Sudo
Cancers 2023, 15(9), 2468; https://doi.org/10.3390/cancers15092468 - 26 Apr 2023
Cited by 2 | Viewed by 1448
Abstract
The combination of the mammalian target of rapamycin and proteasome inhibitors is a new treatment strategy for various tumors. Herein, we investigated the synergistic effect of everolimus and bortezomib on tumor growth and metastasis in bone and soft tissue sarcomas. The antitumor effects [...] Read more.
The combination of the mammalian target of rapamycin and proteasome inhibitors is a new treatment strategy for various tumors. Herein, we investigated the synergistic effect of everolimus and bortezomib on tumor growth and metastasis in bone and soft tissue sarcomas. The antitumor effects of everolimus and bortezomib were assessed in a human fibrosarcoma (FS) cell line (HT1080) and mouse osteosarcoma (OS) cell line (LM8) by MTS assays and Western blotting. The effects of everolimus and bortezomib on HT1080 and LM8 tumor growth in xenograft mouse models were evaluated using tumor volume and the number of metastatic nodes of the resected lungs. Immunohistochemistry was used to evaluate cleaved PARP expression. The combination therapy decreased FS and OS cell proliferation compared with either drug alone. This combination induced more intense p-p38, p-JNK, and p-ERK and activated apoptosis signals, such as caspase-3, compared with single-agent treatment. The combination treatment reduced p-AKT and MYC expression, decreased FS and OS tumor volumes, and suppressed lung metastases of OS. The combination therapy inhibited tumor growth in FS and OS and metastatic progression of OS via the JNK/p38/ERK MAPK and AKT pathways. These results could aid in the development of new therapeutic strategies for sarcomas. Full article
(This article belongs to the Special Issue Soft Tissue Sarcoma: Imaging, Mechanisms and Therapy)
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17 pages, 2059 KiB  
Article
Systemic Inflammatory Indices in Second-Line Soft Tissue Sarcoma Patients: Focus on Lymphocyte/Monocyte Ratio and Trabectedin
by Valentina Fausti, Alessandro De Vita, Silvia Vanni, Virginia Ghini, Lorena Gurrieri, Nada Riva, Roberto Casadei, Marco Maraldi, Giorgio Ercolani, Davide Cavaliere, Carlo Alberto Pacilio, Federica Pieri, Flavia Foca, Alberto Bongiovanni, Nicoletta Ranallo, Sebastiano Calpona, Giovanni Luca Frassineti, Toni Ibrahim and Laura Mercatali
Cancers 2023, 15(4), 1080; https://doi.org/10.3390/cancers15041080 - 08 Feb 2023
Cited by 12 | Viewed by 1668
Abstract
A second-line standard of treatment has not yet been identified in patients with soft tissue sarcomas (STS), so identifying predictive markers could be a valuable tool. Recent studies have shown that the intratumoral and inflammatory systems significantly influence tumor aggressiveness. We aimed to [...] Read more.
A second-line standard of treatment has not yet been identified in patients with soft tissue sarcomas (STS), so identifying predictive markers could be a valuable tool. Recent studies have shown that the intratumoral and inflammatory systems significantly influence tumor aggressiveness. We aimed to investigate prognostic values of pre-therapy neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory index (SII), progression-free survival (PFS), and overall survival (OS) of STS patients receiving second-line treatment. In this single-center retrospective analysis, ninety-nine patients with STS were enrolled. All patients received second-line treatment after progressing to anthracycline. PFS and OS curves were calculated using the Kaplan–Meier method of RNA sequencing, and CIBERSORT analysis was performed on six surgical specimens of liposarcoma patients. A high NLR, PLR, and SII were significantly associated with worse PFS (p = 0.019; p = 0.004; p = 0.006). Low LMR was significantly associated with worse OS (p = 0.006). Patients treated with Trabectedin showed a better PFS when the LMR was low, while patients treated with other regimens showed a worse PFS when the LMR was low (p = 0.0154). The intratumoral immune infiltrates analysis seems to show a correlation between intratumoral macrophages and LMR. PS ECOG. The metastatic onset and tumor burden showed prognostic significance for PFS (p = 0.004; p = 0.041; p = 0.0086). According to the histologies, PFS was: 5.7 mo in liposarcoma patients vs. 3.8 mo in leiomyosarcoma patients vs. 3.1 months in patients with other histologies (p = 0.053). Our results confirm the prognostic role of systemic inflammatory markers in patients with STS. Moreover, we demonstrated that LMR is a specific predictor of Trabectedin efficacy and could be useful in daily clinical practice. We also highlighted a possible correlation between LMR levels and the percentage of intratumoral macrophages. Full article
(This article belongs to the Special Issue Soft Tissue Sarcoma: Imaging, Mechanisms and Therapy)
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13 pages, 1393 KiB  
Article
Comparing Apparent Diffusion Coefficient and FNCLCC Grading to Improve Pretreatment Grading of Soft Tissue Sarcoma—A Translational Feasibility Study on Fusion Imaging
by Madelaine Hettler, Julia Kitz, Ali Seif Amir Hosseini, Manuel Guhlich, Babak Panahi, Jennifer Ernst, Lena-Christin Conradi, Michael Ghadimi, Philipp Ströbel and Jens Jakob
Cancers 2022, 14(17), 4331; https://doi.org/10.3390/cancers14174331 - 05 Sep 2022
Cited by 3 | Viewed by 2841
Abstract
Histological subtype and grading are cornerstones of treatment decisions in soft tissue sarcoma (STS). Due to intratumoral heterogeneity, pretreatment grading assessment is frequently unreliable and may be improved through functional imaging. In this pilot study, 12 patients with histologically confirmed STS were included. [...] Read more.
Histological subtype and grading are cornerstones of treatment decisions in soft tissue sarcoma (STS). Due to intratumoral heterogeneity, pretreatment grading assessment is frequently unreliable and may be improved through functional imaging. In this pilot study, 12 patients with histologically confirmed STS were included. Preoperative functional magnetic resonance imaging was fused with a computed tomography scan of the resected specimen after collecting core needle biopsies and placing radiopaque markers at distinct tumor sites. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading criteria of the biopsies and apparent diffusion coefficients (ADCs) of the biopsy sites were correlated. Concordance in grading between the specimen and at least one biopsy was achieved in 9 of 11 cases (81.8%). In 7 of 12 cases, fusion imaging was feasible without relevant contour deviation. Functional analysis revealed a tendency for high-grade regions (Grade 2/3 (G2/G3)) (median (range) ± standard deviation: 1.13 (0.78–1.70) ± 0.23 × 10−3 mm2/s) to have lower ADC values than low-grade regions (G1; 1.43 (0.64–2.03) ± 0.46 × 10−3 mm2/s). In addition, FNCLCC scoring of multiple tumor biopsies proved intratumoral heterogeneity as expected. The ADC appears to correlate with the FNCLCC grading criteria. Further studies are needed to determine whether functional imaging may supplement histopathological grading. Full article
(This article belongs to the Special Issue Soft Tissue Sarcoma: Imaging, Mechanisms and Therapy)
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Review

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17 pages, 16231 KiB  
Review
CT and MR Imaging of Retroperitoneal Sarcomas: A Practical Guide for the Radiologist
by Giorgia Porrello, Roberto Cannella, Angelo Randazzo, Giuseppe Badalamenti, Giuseppe Brancatelli and Federica Vernuccio
Cancers 2023, 15(11), 2985; https://doi.org/10.3390/cancers15112985 - 30 May 2023
Cited by 3 | Viewed by 3872
Abstract
Primary retroperitoneal sarcomas (RPS) represent around 10–16% of all sarcomas, with liposarcomas and leiomyosarcomas being the most common subtypes. RPS have some peculiar characteristics, imaging appearances, worse prognosis, and complications compared to other locations of sarcoma. Commonly, RPS primarily present as large masses, [...] Read more.
Primary retroperitoneal sarcomas (RPS) represent around 10–16% of all sarcomas, with liposarcomas and leiomyosarcomas being the most common subtypes. RPS have some peculiar characteristics, imaging appearances, worse prognosis, and complications compared to other locations of sarcoma. Commonly, RPS primarily present as large masses, progressively encasing adjacent structures, causing mass effect, and complications. RPS diagnosis is often challenging, and these tumors may be overlooked; however, failure to recognize RPS characteristics leads to a worse prognosis for the patients. Surgery is the only recognized curative treatment, but the anatomical constraints of the retroperitoneum limit the ability to achieve wide resection margins; therefore, these tumors have a high rate of recurrence, and require long-term follow-up. The radiologist has an important role in the diagnosis of RPS, the definition of their extent, and their follow-up. Specific knowledge of the main imaging findings is required to reach an early diagnosis, and, ultimately, to guarantee the best patient management. This article provides an overview of the current knowledge regarding cross-sectional imaging features of patients with retroperitoneal sarcomas, presenting tips and tricks to improve imaging diagnosis of RPS. Full article
(This article belongs to the Special Issue Soft Tissue Sarcoma: Imaging, Mechanisms and Therapy)
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