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Special Issue "Innovations in Soft Tissue Sarcoma Diagnosis and Treatment"

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: 15 December 2023 | Viewed by 5418

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Special Issue Editors

Dr. Erlinda M. Gordon

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Guest Editor

Sarcoma Oncology Research Center, Santa Monica, CA 90403, USA
Interests: sarcoma; gene therapy; natural killer cell therapy; immune and cell-cycle checkpoint inhibitors; tumor targeting

Dr. Sant P. Chawla

E-Mail Website
Guest Editor

Sarcoma Oncology Research Center, Santa Monica, CA 90403, USA
Interests: sarcoma; gene therapy; natural killer cell therapy; immune and cell-cycle checkpoint inhibitors; tumor targeting

Dr. Frederick L. Hall
E-Mail Website
Guest Editor

Sarcoma Oncology Research Center, Santa Monica, CA 90403, USA
Interests: cancer gene therapy; targeted gene delivery; cyclin G1; oncogenic drivers along the CCNG1 pathway; retroviral vector cloning; targeting pharmaceutical agents to injured tissues

Special Issue Information

Dear Colleagues,

Recent advances in genetic screening, molecular profiling, targeted therapy, gene therapy and immunotherapy for soft tissue sarcomas (STS) have evoked increasing optimism in the medical and scientific community. Hence, it is time to reflect on the many faces of STS and current innovations in its diagnosis and treatment. STS is a rare cancer involving mesodermal tissues. Surgical resection is the standard of care for localized disease, but its recurrence rate is high and the prognosis for advanced STS is poor, with a median survival of 8–13 months.

This Special Issue entitled "Innovations in Soft Tissue Sarcoma Diagnosis and Treatment" will include review articles, original clinical and translational research articles that are hypothesis-generating toward the development of precision medicine for STS.

Dr. Erlinda M. Gordon
Dr. Sant P. Chawla
Dr. Frederick L. Hall
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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 2600 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
gene therapy
natural killer cell therapy
immune and cell-cycle checkpoint inhibitors
targeted therapy
Genetics
Genomics
Surgery
Radiologic Imaging

Published Papers (5 papers)

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Research

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Open AccessArticle

SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced Soft Tissue Sarcoma

Victoria S. Chua-Alcala

and

Cancers 2023, 15(3), 906; https://doi.org/10.3390/cancers15030906 - 31 Jan 2023

Cited by 2 | Viewed by 1148

Abstract

Background: This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma. Methods: Phase I endpoints—maximum tolerated dose in previously treated patients; Phase II endpoints—best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments—escalating doses of trabectedin (1.0, 1.2, 1.5 mg/m²) as continuous intravenous infusion over 24 h every 3 weeks, 1 mg/kg of ipilimumab given intravenously every 12 weeks, and 3 mg/kg of nivolumab given intravenously every 2 weeks; Phase II treatments—maximum tolerated dose of trabectedin and defined doses of ipilimumab and nivolumab. Results: Phase I (n = 9)—the maximum tolerated dose of trabectedin was 1.2 mg/m²; Phase II (n = 79)—6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median progression-free survival, 6.7 months (CI 95%: 4.4–7.9), median overall survival, 24.6 months (CI 95%: 17.0–.); Grade 3/4 therapy-related adverse events (n = 92)—increased ALT (25%), fatigue (8.7%), increased AST (8.7%), decreased neutrophil count (5.4%) and anemia (4.6%). Conclusion: SAINT is a safe and effective first-line treatment for advanced soft tissue sarcoma. Full article

(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)

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Open AccessArticle

Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging

and

Cancers 2023, 15(3), 582; https://doi.org/10.3390/cancers15030582 - 18 Jan 2023

Viewed by 937

Abstract

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0–2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon’s clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28–83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful. Full article

(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)

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Review

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Open AccessReview

Targeting the Molecular and Immunologic Features of Leiomyosarcoma

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Cancers 2023, 15(7), 2099; https://doi.org/10.3390/cancers15072099 - 31 Mar 2023

Viewed by 1044

Abstract

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, and DNA damage response pathways that may contribute to resistance against immune-checkpoint blockade monotherapy. The LMS immune microenvironment is highly infiltrated with tumor-associated macrophages and tumor-infiltrating lymphocytes, which may represent promising biomarkers. This review provides an overview of the clinical and pathologic behavior of both soft tissue and uterine LMS and summarizes the genomic and immune characteristics of these tumors and how they may provide opportunities for the development of biomarker-based immune therapies. Full article

(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)

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Open AccessReview

The Next Frontier in Sarcoma: Molecular Pathways and Associated Targeted Therapies

Ted Kim

and

Nam Q. Bui

Cancers 2023, 15(6), 1692; https://doi.org/10.3390/cancers15061692 - 09 Mar 2023

Viewed by 679

Abstract

Soft tissue sarcomas (STS) are a rare, complex, heterogeneous group of mesenchymal neoplasms with over 150 different histological subtypes. Treatments for this malignancy have been especially challenging due to the heterogeneity of the disease and the modest efficacy of conventional chemotherapy. The next frontier lies in discerning the molecular pathways in which these mesenchymal neoplasms arise, metastasize, and develop drug-resistance, thereby helping guide new therapeutic targets for the treatment of STS. This comprehensive review will discuss the current understanding of tumorigenesis of specific STS subtypes, including oncogenic pathway alterations involved in cell cycle regulation, angiogenesis, NOTCH signaling, and aberrant genetic rearrangements. It will then review current therapies that have been recently developed to target these pathways, including a review of ongoing clinical studies for targeted sarcoma treatment, as well as discuss new potential avenues for therapies against known molecular pathways of sarcomagenesis. Full article

(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)

Open AccessReview

Imaging Hallmarks of Sarcoma Progression Via X-ray Computed Tomography: Beholding the Flower of Evil

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Cancers 2022, 14(20), 5112; https://doi.org/10.3390/cancers14205112 - 19 Oct 2022

Viewed by 1083

Abstract

Sarcomas are a leading cause of cancer death in individuals younger than 20 years of age and represent the largest group of rare solid tumors. To date, more than 100 morphological subtypes of sarcomas have been described, among which epidemiology, clinical features, management, and prognosis differ significantly. Delays and errors in the diagnosis of sarcomas limit the number of effective therapeutic modalities and catastrophically worsen the prognosis. Therefore, the development of an algorithm for the early accurate diagnosis of sarcomas seems to be as important as the development of novel therapeutic advances. This literature review aims to summarize the results of recent investigations regarding the imaging of sarcoma progression based on the use of X-ray computed tomography (CT) in preclinical studies and in current clinical practice through the lens of cancer hallmarks. We attempted to summarize the main CT imaging features of soft-tissue and bone sarcomas. We noted the development of new molecular markers with high specificity to antibodies and chemokines, which are expressed in particular sarcoma subtypes to reach tumor type-specific imaging. We demonstrate the possibility of the use of X-ray computed microtomography (micro-CT) for non-destructive 3D visualization of solid tumors by increasing the visibility of soft tissues with X-ray scattering agents. Based on the results of recent studies, we hypothesize that micro-CT enables the visualization of neovascularization and stroma formation in sarcomas at high-resolution in vivo and ex vivo, including the novel techniques of whole-block and whole-tissue imaging. Finding correlations between CT, PET/CT, and micro-CT imaging features, the results of the histopathological specimen examination and clinical outcomes may significantly increase the accuracy of soft-tissue and bone tumor diagnostics, which leads to the initiation of appropriate histotype-specific management in a timely manner and, consequently, to improved outcomes. Full article

(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)

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