Multimodality Management of Sarcomas

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

Deadline for manuscript submissions: closed (10 June 2024) | Viewed by 21205

Special Issue Editors


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Guest Editor
1. Department of Medical Oncology, Centre Léon Bérard, 69008 Lyon, France
2. Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 69373 Lyon, France
Interests: sarcomas; breast cancer; renal cell carcinoma

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Guest Editor
Department of Surgical Oncology, Medical School of Crete University Hospital, Heraklion, Greece
Interests: sarcoma; melanoma; breast cancer; colorectal cancer, peritoneal carcinomatosis; intraperitoneal chemotherapy; HIPEC

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Guest Editor
1. Center for Orthopedic and Trauma Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
2. Rhein-Main Sarcoma Center at University Cancer Center, University Medical Center of Mainz, Mainz, Germany
Interests: orthopedic surgery; orthopedic oncology; bone sarcoma; soft tissue sarcoma; pathological fractures; metastatic disease; benign bone tumours and tumour-like lesions; osteology; benign soft tissue tumors

Special Issue Information

Dear Colleagues,

Due to their rarity and heterogeneity, with a wide variety of histological subtypes, biological behaviors and tumor localization, the optimal management of sarcomas remains challenging. The treatment of sarcomas has to be individualized and consists, usually, of a combination of modalities. Currently, sarcomas are managed in a multimodality manner.

Initial appropriate imaging is of outmost importance to demonstrate the exact localization and extension of the tumor and its relation to adjacent structures, in order to facilitate the performance of a diagnostic core needle biopsy and the planning of a surgical procedure when systemic disease is excluded. A preoperative biopsy is of outmost importance to differentiate between benign and malignant tumors and to define the sarcoma subtype. The pathological examination of those rare and heterogenous sarcoma tumors is very demanding and expertise is required. The treatment plan of each sarcoma is personalized according to its imaging and pathology.

Until recently, most extremity soft tissue sarcomas were locally treated with amputation; nowadays, the majority of patients receive a limb-salvage treatment with a wide excision of the tumor and radiotherapy. Current evidence shows that preoperative radiotherapy may be preferred over the typical postoperative radiotherapy, whereas in low-risk patients radiotherapy may even be omitted. In selected cases, preoperative systemic chemotherapy or isolated limb perfusion may be indicated in an attempt to preserve the extremity. For retroperitoneal sarcomas, recently, a more aggressive surgical approach has been advocated for, whereas the exact role of preoperative radiotherapy or chemotherapy to facilitate resection and to reduce the high risk of local recurrence has still to be defined. The systemic therapy of soft tissue sarcomas, either as an adjuvant treatment or for metastatic disease, has evolved from the classical anthracycline-based regime, to a more individualized histology-driven chemotherapy, whereas novel drugs have been developed. Bone sarcomas are usually also managed in a multimodality manner, depending on the histological type. Although localized chondrosarcomas are initially treated by surgical excision and/or radiotherapy, Ewing sarcomas are traditionally treated with systemic chemotherapy, followed by a local treatment, including surgery and/or radiotherapy, and the continuation of systemic chemotherapy. Similarly, osteosarcomas are usually treated with a combination of chemotherapy and surgery, with or without radiotherapy and the continuation of chemotherapy.

As this illustrates, the management of sarcomas is challenging and multimodal, including radiology and pathology for initial diagnosis and, subsequently, surgery, and through the use of chemotherapy and/or radiotherapy for definite treatment in order to achieve optimal oncological and functional outcomes. The various aspects of this multimodality management and their current roles will be discussed in this Special Issue.

Prof. Dr. Jean-Yves Blay
Prof. Dr. Eelco de Bree
Prof. Dr. Frank Traub
Guest Editors

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Keywords

  • sarcomas
  • multimodal
  • pathology
  • radiology
  • surgery
  • chemotherapy
  • radiotherapy

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Published Papers (16 papers)

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10 pages, 1718 KiB  
Article
Outcome of Endoprosthetic Hip Reconstruction Following Resection of Malignant Bone Tumors
by Thilo Khakzad, Michael Putzier, Alp Paksoy, Daniel Rau, Leonard Thielscher, Nima Taheri, Silvan Wittenberg and Sven Märdian
Cancers 2024, 16(16), 2890; https://doi.org/10.3390/cancers16162890 - 20 Aug 2024
Viewed by 548
Abstract
Introduction: Over the past few decades, tumor arthroplasty has evolved into an established therapeutic approach for addressing bone defects following tumor resection in the extremities. As the diagnosis has a significant impact on patients’ lives, it is important to give clear expectations for [...] Read more.
Introduction: Over the past few decades, tumor arthroplasty has evolved into an established therapeutic approach for addressing bone defects following tumor resection in the extremities. As the diagnosis has a significant impact on patients’ lives, it is important to give clear expectations for functional recovery. Therefore, we investigated both the functional outcomes and the quality of life (QoL) after tumor arthroplasty for malignant hip tumors. Methods: This retrospective study included patients who had undergone resections of malignant hip tumors with consecutive modular hip arthroplasty between 2010 and 2018. Demographics, tumor entity, and complications stemming from both tumors and treatments were evaluated through the analysis of medical records and perioperative records. The assessment of functional outcomes was conducted with the following patient-reported outcome measures (PROMs): the Harris Hip Score (HHS), Musculoskeletal Tumor Society Score (MSTS), and the Short Form Survey 36 (SF-36). Furthermore, we performed subgroup analysis in two groups: one divided into survivors and non-survivors, as well as younger individuals (<57 years) and older individuals (>57 years). Results: A total of 30 patients were included in the study. At the time of follow-up, 19 patients were deceased. The average duration of follow-up was 3.2 (±2.51) years. The average age at the time of surgery was 60.3 (±15.20) years. Notably, there were no cases of amputation reported (0%). Five cases of implant failure were identified (16.67%). Among these, one was attributed to infection (3.3%), while four resulted from aseptic loosening (13.3%). In terms of functional outcomes, MSTS indicated good results (18 ± 7; range: 7–28; 60%), and the HHS demonstrated moderate outcomes (75.3%). Younger survivors (<57 years) exhibited notably superior results in terms of both the MSTS and physical functioning in the SF-36 (p = 0.03). Conclusion: In summary, this study shows declining tumor arthroplasty-related complications and satisfying functional outcomes as well as QoL. Noteworthy aspects include the relatively low rates of amputation and local tumor recurrences, which significantly favor the selection of appropriate therapeutic options. Moreover, the findings underscore the substantial impact of patients’ age on overall functionality and engagement in daily activities. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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21 pages, 4224 KiB  
Article
Arid1a Loss Enhances Disease Progression in a Murine Model of Osteosarcoma
by Kaniz Fatema, Yanliang Wang, Adriene Pavek, Zachary Larson, Christopher Nartker, Shawn Plyler, Amanda Jeppesen, Breanna Mehling, Mario R. Capecchi, Kevin B. Jones and Jared J. Barrott
Cancers 2024, 16(15), 2725; https://doi.org/10.3390/cancers16152725 - 31 Jul 2024
Viewed by 1137
Abstract
Osteosarcoma is an aggressive bone malignancy, molecularly characterized by acquired genome complexity and frequent loss of TP53 and RB1. Obtaining a molecular understanding of the initiating mutations of osteosarcomagenesis has been challenged by the difficulty of parsing between passenger and driver mutations [...] Read more.
Osteosarcoma is an aggressive bone malignancy, molecularly characterized by acquired genome complexity and frequent loss of TP53 and RB1. Obtaining a molecular understanding of the initiating mutations of osteosarcomagenesis has been challenged by the difficulty of parsing between passenger and driver mutations in genes. Here, a forward genetic screen in a genetic mouse model of osteosarcomagenesis initiated by Trp53 and Rb1 conditional loss in pre-osteoblasts identified that Arid1a loss contributes to OS progression. Arid1a is a member of the canonical BAF (SWI/SNF) complex and a known tumor suppressor gene in other cancers. We hypothesized that the loss of Arid1a increases the rate of tumor progression and metastasis. Phenotypic evaluation upon in vitro and in vivo deletion of Arid1a validated this hypothesis. Gene expression and pathway analysis revealed a correlation between Arid1a loss and genomic instability, and the subsequent dysregulation of genes involved in DNA DSB or SSB repair pathways. The most significant of these transcriptional changes was a concomitant decrease in DCLRE1C. Our findings suggest that Arid1a plays a role in genomic instability in aggressive osteosarcoma and a better understanding of this correlation can help with clinical prognoses and personalized patient care. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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17 pages, 530 KiB  
Article
The Impact of Expert Pathology Review and Molecular Diagnostics on the Management of Sarcoma Patients: A Prospective Study of the Hellenic Group of Sarcomas and Rare Cancers
by Stefania Kokkali, Ioannis Boukovinas, Eelco de Bree, Anna Koumarianou, Vassilis Georgoulias, Anastasios Kyriazoglou, Nikolaos Tsoukalas, Nikolaos Memos, John Papanastassiou, Anastasia Stergioula, Konstantinos Tsapakidis, Konstantia Loga, Jose Duran-Moreno, Panagiotis Papanastasopoulos, Nikolaos Vassos, Vasileios Kontogeorgakos, Ilias Athanasiadis, Luiza Mahaira, Efthymios Dimitriadis, Dionysios J. Papachristou and George Agrogiannisadd Show full author list remove Hide full author list
Cancers 2024, 16(13), 2314; https://doi.org/10.3390/cancers16132314 - 24 Jun 2024
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Abstract
Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the [...] Read more.
Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was performed on all samples using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed in the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary, molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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15 pages, 588 KiB  
Article
Complications and Risk Factors in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy
by Arthur Lebas, Clara Le Fevre, Waisse Waissi, Isabelle Chambrelant, David Brinkert and Georges Noel
Cancers 2024, 16(11), 1977; https://doi.org/10.3390/cancers16111977 - 23 May 2024
Viewed by 948
Abstract
Introduction: Soft tissue sarcomas of the extremities (ESTSs) pose significant challenges in treatment and management due to their diverse nature and potential complications. This study aimed to assess complications associated with multimodal treatments involving surgery and radiotherapy (RT) and to identify potential risk [...] Read more.
Introduction: Soft tissue sarcomas of the extremities (ESTSs) pose significant challenges in treatment and management due to their diverse nature and potential complications. This study aimed to assess complications associated with multimodal treatments involving surgery and radiotherapy (RT) and to identify potential risk factors. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with surgery and pre- or post-operative RT between 2007 and 2020 in Strasbourg, France. Complications, including wound complications (WCs), lymphedema, acute and chronic RT-related complications, and fractures, were meticulously evaluated. Results: A total of 169 patients diagnosed with localized ESTSs were included, with a median age of 64 years (range 21–94 years). ESTSs primarily occurred proximally (74.6%) and in the lower limbs (71%). The median follow-up was 5.5 years. WCs occurred in 22.5% of patients, with proximal and lower extremity tumors being significant risk factors. Acute RT-related complications included radiodermatitis, with grade ≥ 2 occurring in 43.1% of patients, which was associated with superficial tumors. Three patients had an edema grade ≥ 2. Chronic complications included telangiectasias (21.7%) and fibrosis (38.7%), with higher rates associated with larger PTVs and higher RT doses, respectively. Fractures occurred in 5 patients, mainly in the tibia (40%). Conclusions: Multimodal treatment of ESTSs demonstrated excellent tolerance, with manageable side effects. Numerous risk factors have been highlighted, providing insights for optimizing treatment strategies and enhancing patient care in this rare disease. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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12 pages, 537 KiB  
Article
Osteosarcoma Arising as a Secondary Malignancy following Treatment for Hematologic Cancer: A Report of 33 Affected Patients from the Cooperative Osteosarcoma Study Group (COSS)
by Stefan S. Bielack, Vanessa Mettmann, Daniel Baumhoer, Claudia Blattmann, Birgit Burkhardt, Christoph K. W. Deinzer, Leo Kager, Matthias Kevric, Christine Mauz-Körholz, Peter Müller-Abt, Dirk Reinhardt, Alexandru-Anton Sabo, Martin Schrappe, Benjamin Sorg, Reinhard Windhager and Stefanie Hecker-Nolting
Cancers 2024, 16(10), 1836; https://doi.org/10.3390/cancers16101836 - 11 May 2024
Viewed by 1007
Abstract
Purpose: Osteosarcoma may arise as a secondary cancer following leukemias or lymphomas. We intended to increase the knowledge about such rare events. Patients and methods: We searched the Cooperative Osteosarcoma Study Group’s database for individuals who developed their osteosarcoma following a previous hematological [...] Read more.
Purpose: Osteosarcoma may arise as a secondary cancer following leukemias or lymphomas. We intended to increase the knowledge about such rare events. Patients and methods: We searched the Cooperative Osteosarcoma Study Group’s database for individuals who developed their osteosarcoma following a previous hematological malignancy. The presentation and treatment of both malignancies was investigated, and additional neoplasms were noted. Outcomes after osteosarcoma were analyzed and potential prognostic factors were searched for. Results: A total of 33 eligible patients were identified (male: 23, female: 10; median age: 12.9 years at diagnosis of hematological cancer; 20 lymphomas, 13 leukemias). A cancer predisposition syndrome was evident in one patient only. The hematological cancers had been treated by radiotherapy in 28 (1 unknown) and chemotherapy in 26 cases, including bone-marrow transplantation in 9. The secondary bone sarcomas (high-grade central 27, periosteal 2, extra-osseous 2, undifferentiated pleomorphic sarcoma of bone 2) arose after a median lag-time of 9.4 years, when patients were a median of 19.1 years old. Tumors were considered radiation-related in 26 cases (1 unknown). Osteosarcoma-sites were in the extremities (19), trunk (12), or head and neck (2). Metastases at diagnosis affected eight patients. Information on osteosarcoma therapy was available for 31 cases. All of these received chemotherapy. Local therapy involved surgery in 27 patients, with a good response reported for 9/18 eligible patients. Local radiotherapy was given to three patients. The median follow-up was 3.9 (0.3–12.0) years after bone tumor diagnosis. During this period, 21 patients had developed events as defined, and 15 had died, resulting in 5-year event-free and overall survival rates of 40% (standard error: 9%) and 56% (10%), respectively. There were multiple instances of additional neoplasms. Several factors were found to be of prognostic value (p < 0.05) for event-free (osteosarcoma site in the extremities) or overall (achievement of a surgical osteosarcoma-remission, receiving chemotherapy for the hematologic malignancy) survival. Conclusions: We were able to prove radiation therapy for hematological malignancies to be the predominant risk factor for later osteosarcomas. A resulting overrepresentation of axial and a tendency towards additional neoplasms affects prognosis. Still, selected patients may become long-term survivors with appropriate therapies, which is an argument against therapeutic negligence. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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16 pages, 811 KiB  
Article
Factors Influencing Long-Term Local Recurrence, Distant Metastasis, and Survival in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy
by Arthur Lebas, Clara Le Fevre, Waisse Waissi, Isabelle Chambrelant, David Brinkert and Georges Noel
Cancers 2024, 16(10), 1789; https://doi.org/10.3390/cancers16101789 - 7 May 2024
Cited by 4 | Viewed by 1014
Abstract
Introduction: The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. [...] Read more.
Introduction: The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications. Results: A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21–94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2–3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy4 (range 45.0–109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy4 (p = 0.015). Deep tumors were associated with worse OS (p < 0.05), and grade 2–3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS (p < 0.05). IMRT was associated with longer LC than 3DRT (p = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS (p < 0.05) and that patients with distant relapse had shorter OS (p < 0.0001). Conclusion: RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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12 pages, 934 KiB  
Article
Prices and Trends in FDA-Approved Medications for Sarcomas
by Caleb Hwang, Mark Agulnik and Brian Schulte
Cancers 2024, 16(8), 1545; https://doi.org/10.3390/cancers16081545 - 18 Apr 2024
Cited by 1 | Viewed by 1228
Abstract
Sarcomas represent a diverse set of both malignant and benign subtypes consisting of often rare and ultra-rare conditions. Over the course of the last decade, there have been numerous FDA approvals for agents treating various sarcoma subtypes. Given this burgeoning landscape of sarcoma [...] Read more.
Sarcomas represent a diverse set of both malignant and benign subtypes consisting of often rare and ultra-rare conditions. Over the course of the last decade, there have been numerous FDA approvals for agents treating various sarcoma subtypes. Given this burgeoning landscape of sarcoma treatments, we seek to review current FDA-approved agents with respect to their rates of incidence, approval rates, and financial costs. We gathered clinical trial data by searching FDA approval announcements from 2013 to 2023. We determined the 30 day and one year cost of therapy for patients of FDA-approved sarcoma treatments in the aforementioned timeframe. From 2013 to 2023, 14 medications have been FDA-approved for sarcoma subtypes. The 30-day dosing prices for these medications range from $11,162.86 to $46,926.00. Since 2013, the rates of approval for sarcoma medications have been higher than in prior decades. Nonetheless, there remains the potential for significant financial toxicity for patients living with sarcoma. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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15 pages, 2076 KiB  
Article
Improved Metastatic-Free Survival after Systematic Re-Excision Following Complete Macroscopic Unplanned Excision of Limb or Trunk Soft Tissue Sarcoma
by Francois Gouin, Audrey Michot, Mehrdad Jafari, Charles Honoré, Jean Camille Mattei, Alexandre Rochwerger, Mickael Ropars, Dimitri Tzanis, Philippe Anract, Sébastien Carrere, Dimitri Gangloff, Agnès Ducoulombier, Céleste Lebbe, Jérôme Guiramand, Denis Waast, Frédéric Marchal, François Sirveaux, Sylvain Causeret, Pierre Gimbergues, Fabrice Fiorenza, Brice Paquette, Pauline Soibinet, Jean-Marc Guilloit, Louis R. Le Nail, Franck Dujardin, David Brinkert, Claire Chemin-Airiau, Magali Morelle, Pierre Meeus, Marie Karanian, François Le Loarer, Gualter Vaz and Jean-Yves Blayadd Show full author list remove Hide full author list
Cancers 2024, 16(7), 1365; https://doi.org/10.3390/cancers16071365 - 30 Mar 2024
Cited by 3 | Viewed by 1201
Abstract
Background: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) [...] Read more.
Background: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated. Methods: This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE. Results: Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53–0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE. Conclusions: RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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18 pages, 2964 KiB  
Article
Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades
by Maud Toulmonde, Derek Dinart, Mehdi Brahmi, Benjamin Verret, Myriam Jean-Denis, Françoise Ducimetière, Gregoire Desolneux, Pierre Méeus, Jean Palussière, Xavier Buy, Amine Bouhamama, Pauline Gillon, Armelle Dufresne, Clémence Hénon, François Le Loarer, Marie Karanian, Carine Ngo, Simone Mathoulin-Pélissier, Carine Bellera, Axel Le Cesne, Jean Yves Blay and Antoine Italianoadd Show full author list remove Hide full author list
Cancers 2023, 15(17), 4306; https://doi.org/10.3390/cancers15174306 - 28 Aug 2023
Cited by 1 | Viewed by 1323
Abstract
Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by KIT or PDGFRA mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in [...] Read more.
Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors characterized by KIT or PDGFRA mutations. Over three decades, significant changes in drug discovery and loco-regional (LR) procedures have impacted treatment strategies. We assessed the evolution of treatment strategies for metastatic GIST patients treated in the three national coordinating centers of NetSarc, the French network of sarcoma referral centers endorsed by the National Institute of Cancers, from 1990 to 2018. The primary objective was to describe the clinical and biological profiles as well as the treatment modalities of patients with metastatic GIST in a real-life setting, including access to clinical trials and LR procedures in the metastatic setting. Secondary objectives were to assess (1) patients’ outcome in terms of time to next treatment (TNT) for each line of systemic treatment, (2) patients’ overall survival (OS), (3) evolution of patients’ treatment modalities and OS according to treatment access: <2002 (pre-imatinib approval), 2002–2006 (pre-sunitinib approval), 2006–2014 (pre-regorafenib approval), post 2014, and (4) the impact of clinical trials and LR procedures on TNT and OS in the metastatic setting. 1038 patients with a diagnosis of GIST made in one of the three participating centers between 1990 and 2018 were included in the national prospective database. Among them, 492 patients presented metastasis, either synchronous or metachronous. The median number of therapy lines in the metastatic setting was 3 (range 0–15). More than half of the patients (55%) participated in a clinical trial during the course of their metastatic disease and half (51%) underwent additional LR procedures on metastatic sites. The median OS in the metastatic setting was 83.4 months (95%CI [72.7; 97.9]). The median TNT was 26.7 months (95%CI [23.4; 32.3]) in first-line, 10.2 months (95%CI [8.6; 11.8]) in second line, 6.7 months (95%CI [5.3; 8.5]) in third line, and 5.5 months (95%CI [4.3; 6.7]) in fourth line, respectively. There was no statistical difference in OS in the metastatic setting between the four therapeutic periods (log rank, p = 0.18). In multivariate analysis, age, AFIP Miettinen classification, mutational status, surgery of the primary tumor, participation in a clinical trial in the first line and LR procedure to metastatic sites were associated with longer TNT in the first line, whereas age, mitotic index, mutational status, surgery of the primary tumor and LR procedure to metastatic sites were associated with longer OS. This real-life study advocates for early reference of metastatic GIST patients to expert centers to orchestrate the best access to future innovative clinical trials together with LR strategies and further improve GIST patients’ survival. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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Review

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14 pages, 1053 KiB  
Review
The Multimodality Management of Malignant Peripheral Nerve Sheath Tumours
by Remus Seres, Hassan Hameed, Martin G. McCabe, David Russell and Alexander T. J. Lee
Cancers 2024, 16(19), 3266; https://doi.org/10.3390/cancers16193266 - 26 Sep 2024
Viewed by 1157
Abstract
Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that have nerve sheath differentiation and can present at any anatomical site. They can arise from precursor neurofibroma in the context of neurofibromatosis type 1 (NF1) or as de novo and sporadic tumours in [...] Read more.
Malignant peripheral nerve sheath tumours (MPNST) are aggressive sarcomas that have nerve sheath differentiation and can present at any anatomical site. They can arise from precursor neurofibroma in the context of neurofibromatosis type 1 (NF1) or as de novo and sporadic tumours in the absence of an underlying genetic predisposition. The primary therapeutic approach is most often radical surgery, with non-surgical modalities playing an important role, especially in locally advanced or metastatic cases. The aim of multimodality approaches is to optimize both local and systemic control while keeping to a minimum acute and late treatment morbidity. Advances in the understanding of the underlying biology of MPNSTs in both sporadic and NF-1-related contexts are essential for the management and implementation of novel therapeutic approaches. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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14 pages, 1873 KiB  
Review
Mesenchymal Tumor Management: Integrating Surgical and Non-Surgical Strategies in Different Clinical Scenarios
by Laura Samà, Giorgia Amy Rodda, Laura Ruspi, Federico Sicoli, Vittoria D’Amato, Salvatore Lorenzo Renne, Alice Laffi, Davide Baldaccini, Elena Clerici, Pierina Navarria, Marta Scorsetti, Alexia Francesca Bertuzzi, Vittorio Lorenzo Quagliuolo and Ferdinando Carlo Maria Cananzi
Cancers 2024, 16(17), 2965; https://doi.org/10.3390/cancers16172965 - 25 Aug 2024
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Abstract
Mesenchymal tumors originate from mesenchymal cells and can be either benign or malignant, such as bone, soft tissue, and visceral sarcomas. Surgery is a cornerstone treatment in the management of mesenchymal tumors, often requiring complex procedures performed in high-volume referral centers. However, the [...] Read more.
Mesenchymal tumors originate from mesenchymal cells and can be either benign or malignant, such as bone, soft tissue, and visceral sarcomas. Surgery is a cornerstone treatment in the management of mesenchymal tumors, often requiring complex procedures performed in high-volume referral centers. However, the COVID-19 pandemic has highlighted this need for alternative non-surgical approaches due to limited access to surgical resources. This review explores the role of non-surgical treatments in different clinical scenarios: for improving surgical outcomes, as a bridge to surgery, as better alternatives to surgery, and for non-curative treatment when surgery is not feasible. We discuss the effectiveness of active surveillance, cryoablation, high-intensity focused ultrasound, and other ablative techniques in managing these tumors. Additionally, we examine the use of tyrosine kinase inhibitors in gastrointestinal stromal tumors and hypofractionated radiotherapy in soft tissue sarcomas. The Sarculator tool is highlighted for its role in stratifying high-risk sarcoma patients and personalizing treatment plans. While surgery remains the mainstay of treatment, integrating advanced non-surgical strategies can enhance therapeutic possibilities and patient care, especially in specific clinical settings with limitations. A multidisciplinary approach in referral centers is vital to determine the optimal treatment course for each patient. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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28 pages, 398 KiB  
Review
Ibero-American Consensus for the Management of Peritoneal Sarcomatosis: Updated Review and Clinical Recommendations
by Francisco Cristóbal Muñoz-Casares, Javier Martín-Broto, Pedro Cascales-Campos, Juan Torres-Melero, Irene López-Rojo, José Gómez-Barbadillo, Luis González-Bayón, Ana Sebio, César Serrano, Sara Carvalhal, Joaquim Abreu de Souza, Alexandre Souza, Guillermo Flores-Ayala, Luis José Palacios Fuenmayor, Raquel Lopes-Bras, José Antonio González-López, Hugo Vasques and José Manuel Asencio-Pascual
Cancers 2024, 16(15), 2646; https://doi.org/10.3390/cancers16152646 - 25 Jul 2024
Viewed by 1352
Abstract
Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted [...] Read more.
Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts’ voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
15 pages, 2106 KiB  
Review
Understanding the Role of Radio-Sensitizing Nanoparticles in Enhancing Pathologic Response in Soft Tissue Sarcomas
by Anastasia Stergioula, Evaggelos Pantelis, Vasileios Kontogeorgakos, Andreas C. Lazaris and Georgios Agrogiannis
Cancers 2023, 15(23), 5572; https://doi.org/10.3390/cancers15235572 - 24 Nov 2023
Cited by 1 | Viewed by 1214
Abstract
High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results [...] Read more.
High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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23 pages, 2772 KiB  
Review
Retroperitoneal Soft Tissue Sarcoma: Emerging Therapeutic Strategies
by Eelco de Bree, Dimosthenis Michelakis, Ioannis Heretis, Nikolaos Kontopodis, Konstantinos Spanakis, Eleni Lagoudaki, Maria Tolia, Michail Zografakis-Sfakianakis, Christos Ioannou and Dimitrios Mavroudis
Cancers 2023, 15(22), 5469; https://doi.org/10.3390/cancers15225469 - 18 Nov 2023
Cited by 4 | Viewed by 2578
Abstract
Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is usually unfeasible in RPS [...] Read more.
Retroperitoneal soft tissue sarcoma (RPS) is a rare and heterogenous disease for which surgery is the cornerstone of treatment. However, the local recurrence rate is much higher than in soft tissue sarcoma of the extremities since wide resection is usually unfeasible in RPS due to its large size, indistinct tumour borders, anatomical constraints and the thinness of the overlying peritoneum. Local recurrence is the leading cause of death for low-grade RPS, whereas high-grade tumours are prone to distant metastases. In recent decades, the role of emerging therapeutic strategies, such as more extended surgery and (neo)adjuvant treatments to improve oncological outcome in primary localised RPS, has been extensively investigated. In this review, the recent data on the evolving multidisciplinary management of primary localised RPS are comprehensively discussed. The heterogeneity of RPS, with their different histological subtypes and biological behaviour, renders a standard therapeutic ‘one-size-fits-all’ approach inappropriate, and treatment should be modified according to histological type and malignancy grade. There is sufficient evidence that frontline extended surgery with compartmental resection including all ipsilateral retroperitoneal fat and liberal en bloc resection of adjacent organs and structures, even if they are not macroscopically involved, increases local tumour control in low-grade sarcoma and liposarcoma, but not in leiomyosarcoma for which complete macroscopic resection seems sufficient. Additionally, preoperative radiotherapy is not indicated for all RPSs, but seems to be beneficial in well-differentiated liposarcoma and grade I/II dedifferentiated liposarcoma, and probably in solitary fibrous tumour. Whether neoadjuvant chemotherapy is of benefit in high-grade RPS remains unclear from retrospective data and is subject of the ongoing randomised STRASS 2 trial, from which the results are eagerly awaited. Personalised, histology-tailored multimodality treatment is promising and will likely further evolve as our understanding of the molecular and genetic characteristics within RPS improves. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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24 pages, 3352 KiB  
Review
Patient-Derived Organoids as a Promising Tool for Multimodal Management of Sarcomas
by Songfeng Xu, ShihJye Tan and Ling Guo
Cancers 2023, 15(17), 4339; https://doi.org/10.3390/cancers15174339 - 30 Aug 2023
Cited by 5 | Viewed by 1930
Abstract
The management of sarcomas, a diverse group of cancers arising from connective tissues, presents significant challenges due to their heterogeneity and limited treatment options. Patient-derived sarcoma organoids (PDSOs) have emerged as a promising tool in the multimodal management of sarcomas, offering unprecedented opportunities [...] Read more.
The management of sarcomas, a diverse group of cancers arising from connective tissues, presents significant challenges due to their heterogeneity and limited treatment options. Patient-derived sarcoma organoids (PDSOs) have emerged as a promising tool in the multimodal management of sarcomas, offering unprecedented opportunities for personalized medicine and improved treatment strategies. This review aims to explore the potential of PDSOs as a promising tool for multimodal management of sarcomas. We discuss the establishment and characterization of PDSOs, which realistically recapitulate the complexity and heterogeneity of the original tumor, providing a platform for genetic and molecular fidelity, histological resemblance, and functional characterization. Additionally, we discuss the applications of PDSOs in pathological and genetic evaluation, treatment screening and development, and personalized multimodal management. One significant advancement of PDSOs lies in their ability to guide personalized treatment decisions, enabling clinicians to assess the response and efficacy of different therapies in a patient-specific manner. Through continued research and development, PDSOs hold the potential to revolutionize sarcoma management and drive advancements in personalized medicine, biomarker discovery, preclinical modeling, and therapy optimization. The integration of PDSOs into clinical practice can ultimately improve patient outcomes and significantly impact the field of sarcoma treatment. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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12 pages, 576 KiB  
Systematic Review
Stereotactic Radiosurgery in Metastatic Spine Disease—A Systemic Review of the Literature
by Adriana Palacio Giraldo, David Sohm, Johannes Neugebauer, Gianpaolo Leone, Marko Bergovec and Dietmar Dammerer
Cancers 2024, 16(16), 2787; https://doi.org/10.3390/cancers16162787 - 7 Aug 2024
Viewed by 688
Abstract
Background: This study investigated the efficacy of stereotactic radiosurgery (SRS) in managing spinal metastasis. Traditionally, surgery was the primary approach, but SRS has emerged as a promising alternative. Objective: The study aims to evaluate the efficacy of stereotactic radiosurgery in the management of [...] Read more.
Background: This study investigated the efficacy of stereotactic radiosurgery (SRS) in managing spinal metastasis. Traditionally, surgery was the primary approach, but SRS has emerged as a promising alternative. Objective: The study aims to evaluate the efficacy of stereotactic radiosurgery in the management of spinal metastasis in terms of local tumor control, patient survival, and quality of life, identifying both advantages and limitations of SRS. Methods: Through an extensive literature search in PubMed with cross-referencing, relevant full-text-available papers published between 2012 and 2022 in English or German were included. The search string used was “metastatic spine diseases AND SRS OR stereotactic radiosurgery”. Results: There is growing evidence of SRS as a precise and effective treatment. SRS delivers high radiation doses while minimizing exposure to critical neural structures, offering benefits like pain relief, limited tumor growth, and a low complication rate, even for tumors resistant to traditional radiation therapies. SRS can be a primary treatment for certain metastatic cases, particularly those without spinal cord compression. Conclusions: SRS appears to be a preferable option for oligometastasis and radioresistant lesions, assuming there are no contraindications. Further research is necessary to refine treatment protocols, determine optimal radiation dose and fractionation schemes, and assess the long-term effects of SRS on neural structures. Full article
(This article belongs to the Special Issue Multimodality Management of Sarcomas)
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