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News and How Much to Improve in Management of Soft Tissue Sarcomas

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

Deadline for manuscript submissions: 30 June 2026 | Viewed by 11361

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Special Issue Editors

Dr. Vicente Artigas-Raventós

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Guest Editor

Surgery Department, Hospital Universitario Sant Pau, Universidad Autonoma de Barcelona, 08035 Barcelona, Spain
Interests: sarcoma; liposarcoma

Dr. José Manuel Asencio

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Guest Editor

Hepatobiliary Surgery and Liver Transplant Unit, Gregorio Marañón University Hospital, 28007 Madrid, Spain
Interests: sarcoma

Special Issue Information

Dear Colleagues,

Soft tissue sarcomas (STSs) are rare, heterogeneous (>150 subtypes), and of mesenchymal origin. They represent less than 1% of adult tumors and can be located anywhere in the body. Under these conditions, a multidisciplinary approach to sarcomas is mandatory. During the last decades, due to the advancement in chemotherapy and surgical techniques, the survival rate has reached approximately 50% in patients with sarcoma. However, survival rates have not improved during the last 20 years. New biomarkers and therapeutic strategies are necessary to further improve prognosis. Likewise, focus on these patients in reference centers is of vital importance to ensure a correct diagnosis and personalized treatment with a correct incorporation of new diagnostic–therapeutic technologies, and thus to improve the medium- and long-term prognosis of these patients.

We are pleased to invite you to collaborate in this Special Issue of the Soft Tissue Sarcomas. This Special Issue will explore how the sarcomas subgroup relates to the scope of the journal.

In this Special Issue, we propose an approach to the recent progress in diagnosis and treatment and the greater impact on the prognosis of the most prevalent subtypes of sarcomas.

Original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: immunotherapy in sarcomas, IA and sarcomas, 3D imaging in sarcomas, new surgical approaches in sarcomas, pelvic sarcomas, sarcomas of the cava veins and others venous locations, retroperitoneal sarcomas, medical gestion and referent centers in sarcomas, treatment of desmoid tumors, treatment approaches to metastasic sarcomas, the state-of-the-art in the medical management of sarcomas, etc.

We look forward to receiving your contributions.

Dr. Vicente Artigas-Raventós
Dr. José Manuel Asencio
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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 sarcomas
prevalent types
multidisciplinary board
reference centers
news diagnosis methods and treatments
implication of IA and 3D in sarcomas
implication of minimally aggressive surgical techniques

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Published Papers (7 papers)

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Research

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15 pages, 270 KB

Open AccessArticle

Experience of a Referral Center with Desmoid Tumors, Part 2: A Retrospective Analysis of 109 Cases

by Alvarez Alvarez Rosa, Agra Pujol Carolina, Arregui Valles Marta, Alijo Francisco, Fernández Gonzalo Adriana, Gutiérrez Natalia, Lozano Lominchar Pablo, Mata Fernández Cristina, Mediavilla Santos Lydia, Novo Ulrike, Santos Marina, Hernández Torrado Guillermo, Carpintero García Henar and Gutiérrez-Ortiz de la Tabla Ana

Cancers 2026, 18(2), 305; https://doi.org/10.3390/cancers18020305 - 19 Jan 2026

Viewed by 38

Abstract

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort. Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments. Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS. Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

30 pages, 3010 KB

Open AccessArticle

Transcriptomic-Based Classification Identifies Prognostic Subtypes and Therapeutic Strategies in Soft Tissue Sarcomas

by Miguel Esperança-Martins, Hugo Vasques, Manuel Sokolov Ravasqueira, Maria Manuel Lemos, Filipa Fonseca, Diogo Coutinho, Jorge Antonio López, Richard S. P. Huang, Sérgio Dias, Lina Gallego-Paez, Luís Costa, Nuno Abecasis, Emanuel Gonçalves and Isabel Fernandes

Cancers 2025, 17(17), 2861; https://doi.org/10.3390/cancers17172861 - 30 Aug 2025

Cited by 1 | Viewed by 2821

Abstract

Background: Soft tissue sarcomas (STSs) histopathological classification system and the clinical and molecular-based tools that are currently employed to estimate its prognosis have several limitations, impacting prognostication and treatment. Clinically driven molecular profiling studies may cover these gaps and offer alternative tools with superior prognostication capability and enhanced precision and personalized treatment approaches identification ability. Materials and Methods/Results: We performed DNA sequencing (DNA-seq) and RNA sequencing (RNA-seq) to portray the molecular profile of 102 samples of high-grade STS, comprising the three most common STS histotypes. The analysis of RNA-seq data using unsupervised machine learning models revealed previously unknown molecular patterns, identifying four transcriptomic subtypes/clusters (TCs). This TC-based classification has a clear prognostic value (in terms of overall survival (OS) and disease-free survival (DFS)), a finding that was externally validated using independent patient cohorts. The prognostic value of this TC-based classification outperforms the prognostic accuracy of clinical-based (SARCULATOR nomograms) and molecular-based (CINSARC) prognostication tools, being one of the first molecular-based classifications capable of predicting OS in STS. The analysis of DNA-seq data from the same cohort revealed numerous and, in some cases, never documented molecular targets for precision treatment across different transcriptomic subtypes. The functional and predictive value of each genomic variant was analyzed using the Molecular Tumor Board Portal. Conclusions: This newly identified TC-based classification offers a superior prognostic value when compared with current gold-standard clinical and molecular-based prognostication tools, and identifies novel molecular targets for precision treatment, representing a cutting-edge tool for predicting prognosis and guiding treatment across different stages of STS. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

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17 pages, 3819 KB

Open AccessArticle

DNA Damage Repair Pathway Alterations and Immune Landscape Differences in Pediatric/Adolescent, Young Adult (AYA) and Adult Sarcomas

by Kurt Statz-Geary, Andrew Elliott, Steven Bialick, César Serrano, Margaret von Mehren, Matthew Oberley, Andrea P. Espejo-Freire, Priscila Barreto Coelho, Philippos A. Costa, Gina Z. D’Amato, Emily Jonczak, Jonathan C. Trent, Elizabeth Montgomery, David Lombard, Andrew Rosenberg and Aditi Dhir

Cancers 2025, 17(12), 1962; https://doi.org/10.3390/cancers17121962 - 12 Jun 2025

Cited by 2 | Viewed by 1743

Abstract

Background: DNA damage response (DDR) pathway alterations contribute to genomic instability and malignant progression in several cancers. Methods: We retrospectively reviewed molecular profiles from 5309 sarcoma patient samples, including 746 from pediatric/adolescent and young adults (ped/AYA), encompassing 38 histologic subtypes. The gene expression profiles were further analyzed for immunotherapy-related biomarker associations, including analysis of the T cell-inflamed score. Results: Pathogenic/likely pathogenic DDR alterations were detected in 15.9% (N = 842) of samples overall and 9.25% (N = 69) of Ped/AYA tumors, with mutations occurring most frequently in ATRX (10.1%). Shorter overall survival was observed for patients with DDR-alterations compared to those with DDR-wildtype tumors (Hazard Ratio = 1.172, 95% CI: 1.068–1.287; p < 0.001). In many subtypes, DDR-mutated tumors were found to have increased rates of immune markers, including PD-L1+, dMMR/MSI-high, and TMB. Conclusions: Our study of somatic DDR-pathway mutations provides a better understanding of the molecular associations across sarcoma subtypes that may aid in developing future prognostic and therapeutic options for these rare cancers. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

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12 pages, 1022 KB

Open AccessArticle

Impact of Severe Postoperative Complications and P-POSSUM Score on Oncological Outcomes in Primary Retroperitoneal Sarcoma: Insights from a Tertiary Cancer Center

by Carlo Abatini, Lorenzo Barberis, Claudio Lodoli, Federica Ferracci, Enrico De Lorenzis, Giorgio D’Annibale, Matteo Aulicino, Michela Quirino, Mariantonietta Di Salvatore, Sergio Alfieri, Fabio Pacelli and Francesco Santullo

Cancers 2025, 17(11), 1787; https://doi.org/10.3390/cancers17111787 - 27 May 2025

Cited by 1 | Viewed by 1620

Abstract

Background: RPS are rare tumors requiring complex surgery. The impact of postoperative complications on long-term outcomes is still debated. This study aimed to identify predictors of severe complications and assess their influence on overall survival (OS) and disease-free survival (DFS). Methods: We retrospectively analyzed 61 patients who underwent curative surgery for primary RPS between 2013 and 2023 at a tertiary cancer center. Patients with pelvic or recurrent sarcomas were excluded. Severe complications were defined as Clavien–Dindo (CD) grade ≥ 3A. Cox regression and Fine–Gray competing risk models were used for OS and DFS, respectively. Sarculator and P-POSSUM scores were included in multivariable models. Results: Severe complications occurred in 14.8% of patients; 30-day mortality was 1.6%. Predictive factors for complications included longer operative time, gastric resection, intraoperative complications, and transfusions. In multivariable analysis, Sarculator was significantly associated with both DFS (HR 0.97; p = 0.004) and OS (HR 0.97; p = 0.008). The P-POSSUM mortality score predicted OS (HR 1.12; p = 0.002). Severe complications were not independently associated with DFS or OS. Conclusions: In this cohort, severe complications did not impact long-term oncological outcomes. Prognostic tools such as Sarculator and P-POSSUM may enhance risk stratification in RPS surgery. Prospective validation is warranted. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

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Review

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19 pages, 1661 KB

Open AccessReview

Desmoid Tumors—Experience from a Referral Center, Part 1: Multidisciplinary Review and Practical Recommendations

by Alvarez Alvarez Rosa, Agra Pujol Carolina, Arregui Valles Marta, Alijo Francisco, Fernández Gonzalo Adriana, Gutiérrez Natalia, Lozano Lominchar Pablo, Mata Fernández Cristina, Mediavilla Santos Lidia, Novo Ulrike, Santos Marina, Hernández Torrado Guillermo, Carpintero García Henar and Gutiérrez-Ortiz de la Tabla Ana

Cancers 2025, 17(21), 3470; https://doi.org/10.3390/cancers17213470 - 29 Oct 2025

Cited by 1 | Viewed by 1566

Abstract

Desmoid tumors (DTs), also known as aggressive fibromatosis, are rare neoplasms characterized by local invasiveness and a high risk of recurrence, despite their lack of metastatic potential. The management of these tumors remains challenging due to their unpredictable behavior and heterogeneous presentations. In this two-part study, we first provide a comprehensive review of the scientific evidence on diagnosis and emerging therapeutic strategies for DT. In the second part, we will present a retrospective analysis of our experience at a national reference center for sarcoma treatment, focusing on diagnostic strategies, therapeutic interventions, and clinical outcomes. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

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16 pages, 459 KB

Open AccessSystematic Review

First-Line Chemotherapy Regimens for Advanced and Metastatic Leiomyosarcoma: Doxorubicin vs. Gemcitabine—A Systematic Review

by Ilma Khan, Priyal Agarwal, Nassar El Assaad, Ravin Ratan and Elise F. Nassif Haddad

Cancers 2026, 18(2), 335; https://doi.org/10.3390/cancers18020335 - 21 Jan 2026

Abstract

Background: Leiomyosarcomas are an aggressive soft-tissue sarcoma that arise from smooth muscle, have a high metastatic potential and account for 10–20% of soft-tissue sarcomas. Despite decades of research, the first-line treatment remains unresolved due to the absence of direct comparative trials, heterogeneous study designs, and trade-offs between efficacy and toxicity. This systematic review evaluates the optimal therapeutic systemic chemotherapy regimens in the first-line setting, specifically gemcitabine- and doxorubicin-based regimens, including associated toxicities. Methods: A systematic search in MEDLINE (Ovid), Embase (Ovid), and Cochrane Library (Wiley) identified studies of first-line gemcitabine- or doxorubicin-based chemotherapy for leiomyosarcoma. The review protocol was registered in PROSPERO (CRD420261280028). Of the 3092 articles screened, 11 articles were eligible for inclusion, comprising results from 1225 patients. Eligible studies were in English and included ≥10 patients with advanced/metastatic leiomyosarcoma reporting on LMS-specific outcomes and no prior systemic therapy. This qualitative systematic review synthesizes prospective and retrospective evidence without quantitative meta-analysis. Results: The review included two phase 3 trials, six phase 2 trials, one phase 1b trial, and two retrospective studies. While there was no direct comparison in this setting, doxorubicin-based combinations consistently reported higher objective response rates, progression-free survival, and overall survival. The most favorable outcomes were observed in the LMS04 trial with doxorubicin plus trabectedin followed by surgery and trabectedin maintenance, yielding a median progression-free survival of 12 months, overall survival of 33 months, and objective response rate of 36%. This regimen also had the highest grade 3–4 toxicity. Conclusions: Doxorubicin-based regimens remain the most active first-line option for leiomyosarcoma, although treatment practices remain heterogeneous. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

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29 pages, 342 KB

Open AccessGuidelines

Ibero-American Consensus for the Management of Liver Metastases of Soft Tissue Sarcoma: Updated Review and Clinical Recommendations

by Raquel Lopes-Brás, Paula Muñoz, Eduardo Netto, Juan Ángel Fernández, Mario Serradilla-Martín, Pablo Lozano, Miguel Esperança-Martins, Gerardo Blanco-Fernández, José Antonio González-López, Francisco Cristóbal Muñoz-Casares, Isabel Fernandes, José Manuel Asencio-Pascual and Hugo Vasques

Cancers 2025, 17(8), 1295; https://doi.org/10.3390/cancers17081295 - 11 Apr 2025

Viewed by 2751

Abstract

Liver metastases from soft tissue sarcoma (STS) (excluding gastrointestinal stromal tumors) are rare and more commonly arise from retroperitoneal and intra-abdominal primary sites. Chemotherapy remains the mainstay of treatment for disseminated disease, but its effectiveness is limited and patients typically have a dismal prognosis with short survival. However, when metastases are confined to the liver (without pulmonary involvement), some patients may benefit from local techniques, either surgical or nonsurgical, that can provide long periods of disease-free survival. Due to the rarity of STS, especially with liver metastases, and the heterogeneity of histologies and biological behavior, there is a lack of standardized treatment guidelines and universally accepted criteria for this specific setting. To fill this gap, a multidisciplinary working group of experts in sarcoma and liver surgery reviewed the literature and available evidence and developed a set of clinical recommendations to be voted and discussed in the I Ibero-American Consensus on the Management of Metastatic Sarcoma, held at the III Spanish-Portuguese Update Meeting on the Treatment of Sarcomas in May 2024. Herein, the voting results of this meeting and the resulting consensus recommendations are presented, and their applicability, strengths, and limitations are discussed. Full article

(This article belongs to the Special Issue News and How Much to Improve in Management of Soft Tissue Sarcomas)

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