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Gómez-Álvarez J, Lamo-Espinosa JM, San-Julián M. Do Patients Treated With an Unplanned Resection for Small Superficial Soft Tissue Sarcomas Have Worse Long-term Survival Than Those Initially Treated With an Oncologic Resection? Clin Orthop Relat Res 2024; 482:00003086-990000000-01483. [PMID: 38277495 PMCID: PMC11124722 DOI: 10.1097/corr.0000000000002974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 11/08/2023] [Indexed: 01/28/2024]
Abstract
BACKGROUND Histologic grade, size, and depth are well-known prognostic factors in soft tissue sarcomas (STS). Small (< 5 cm) and superficial STS generally have an excellent prognosis when treated with appropriate surgery. However, they are often misdiagnosed and mistreated. We reported that in midterm follow-up (5 to 7 years), patients with unplanned resections of tumors with positive margins who immediately underwent a reoperation with margin-widening re-resection and postoperative radiotherapy had survival comparable to that of patients who were initially treated correctly. In that article, we included STS larger than 5 cm, deep STS, and individuals with local recurrence. However, we wanted to evaluate the impact of unplanned resection on the survival of patients who had STS with the best prognosis, small and superficial STS, with two groups that were as homogeneous as possible. QUESTION/PURPOSE Do patients with small and superficial STS who underwent an unplanned resection have worse prognosis in the long term than those who were initially treated correctly? METHODS We exclusively evaluated patients with small (< 5 cm) and superficial (to the deep fascia) STS. We systematically excluded deep STS. Among this subset, we identified 93 patients with superficial STS. We excluded patients with local relapse, metastatic disease, superficial STS of the head or neck, those with insufficient clinical or dosimetric information, and patients with follow-up of less than 2 years. Furthermore, our focus on investigating the most benign and homogeneous STS prompted us to exclude patients with superficial tumors greater than or equal to 5 cm. This selection was driven by the presumed better prognosis associated with smaller tumors, inevitably leading to a smaller pool of patients for direct comparison with patients who had unplanned resections. The initial expectation was to observe similar survival outcomes between cohorts. Between 1990 and 2019, a total of 17 patients underwent surgical treatment at our private, medium-size center. Of those, 29% (5 patients) were lost to follow-up before 2 years without meeting a study endpoint (relapse, metastasis or revision, reoperation, or death), leaving a total of 71% (12 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with surgery alone. During that same period, another 51 patients were referred to us after undergoing an unplanned resection of a lesion that subsequently was determined to be a soft tissue malignancy. Of those, 18% (9 patients) were lost to follow-up before 2 years without meeting a study endpoint, leaving 82% (42 patients) of the original group who had either follow-up of at least 2 years or who met a study endpoint before that minimum surveillance duration. They were treated with re-excision and postoperative radiotherapy. Patients with unplanned resections had an older mean age (51± 5 versus 44 ± 7 years; p = 0.1) and a higher proportion of female patients (58% versus 38%; p = 0.07), but the groups did not differ in terms of largest diameter, histologic type, or tumor location. However, patients with planned resections had a higher proportion of high-grade STS (75% versus 55%; p = 0.07). No metastases were present in either group at diagnosis. We performed a univariate analysis of the groups. We could not perform a multivariate analysis because of the small sample. We compared the groups in terms of local recurrence and all-cause mortality using the Kaplan-Meier survivorship estimator. RESULTS According to the Kaplan-Meier survivorship estimator, survivorship free from local recurrence at a mean of 20 years of follow-up was better in the planned resection group than in the unplanned resection group (92% [95% CI 63% to 100%] versus 69% [95% CI 54% to 81%]; p = 0.04). Furthermore, overall survivorship at 5 years was higher in the planned resection group than in the unplanned resection group (100% [95% CI 72% to 100%] versus 70% [95% CI 54% to 81%]; p = 0.04). Similarly, the planned resection group exhibited superior survivorship at 20 years of follow-up (100% [95% CI 72% to 100%] versus 62% [95% CI 47% to 75%]; p = 0.01). Metastatic disease was absent in the planned resection group, while it occurred in 12 patients in the unplanned resection group (28% [95% CI 17% to 44%]). CONCLUSION Unplanned resection for patients with small and superficial STS was associated with a decrease in overall survival in the long term, despite the use of postoperative radiotherapy. An unplanned resection may be an important prognostic factor. Nevertheless, larger and prospective studies are needed to validate our findings. Although small and superficial lumps are usually benign, nonsarcoma surgeons should be aware that some masses may be malignant, and if in doubt, MR imaging, a biopsy before excision, or consultation with or referral to a sarcoma center should be considered before removing the mass. LEVEL OF EVIDENCE Level III, therapeutic study.
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Affiliation(s)
- Jorge Gómez-Álvarez
- Department of Orthopedic Surgery, Clínica Universidad de Navarra, Pamplona, Spain
| | | | - Mikel San-Julián
- Department of Orthopedic Surgery, Clínica Universidad de Navarra, Pamplona, Spain
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Aiba H, Miwa S, Murakami H, Kimura H. Special Issue: "Pediatric Orthopedic Malignancy: Types, Symptoms, and Treatment". CHILDREN (BASEL, SWITZERLAND) 2023; 10:1545. [PMID: 37761506 PMCID: PMC10527715 DOI: 10.3390/children10091545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023]
Abstract
Pediatric orthopedic malignancies are extremely rare and require appropriate diagnosis and treatment by a multidisciplinary team [...].
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Affiliation(s)
- Hisaki Aiba
- Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan; (H.M.); (H.K.)
| | - Shinji Miwa
- Department of Orthopedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan;
| | - Hideki Murakami
- Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan; (H.M.); (H.K.)
| | - Hiroaki Kimura
- Department of Orthopedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan; (H.M.); (H.K.)
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García-Domínguez DJ, Sánchez-Margalet V, de la Cruz-Merino L, Hontecillas-Prieto L. Knowing the myeloid-derived suppressor cells : Another enemy of sarcomas patients. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2023; 375:93-116. [PMID: 36967155 DOI: 10.1016/bs.ircmb.2022.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Sarcomas are heterogeneous and aggressive malignant tumors with variable responses to current standard treatments being usually incurable for those patients with metastatic and unresectable diseases. The lack of curative strategies has led to develop new therapies in the treatment of sarcomas where the role of immune system is an evolving field. Most sarcomas often exhibit an immunosuppressive microenvironment, which reduces their capacity to trigger an immune response. Therefore, sarcomas are broadly considered as an "immune cold" tumor, although some studies have described a great immune heterogeneity across sarcoma subtypes. Sarcoma cells, like other tumors, evade their immune destruction through a variety of mechanisms, including expansion and recruitment of myeloid derived suppressor cells (MDSCs). MDSCs are immature myeloid cells that have been correlated with a reduction of the therapeutic efficacy, including immunotherapy, tumor progression and worst prognosis. Consequently, different strategies have been developed in recent years to target MDSCs in cancer treatments. This chapter discusses the role of MDSCs in sarcomas and their current potential as a therapeutic target in these malignancies.
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Ajmal Z, Khan AM, Zahra FT, McCarthy L, O’Malley R, Mehdi S. Leiomyosarcoma of the Penis: A Case Report and Re-Appraisal. Fed Pract 2022; 39:S58-S61. [PMID: 35929007 PMCID: PMC9346577 DOI: 10.12788/fp.0232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
BACKGROUND Penile leiomyosarcoma arises from smooth muscles, which can be from dartos fascia, erector pili in the skin covering the shaft, or from tunica media of the superficial vessels and cavernosa. We describe presentation, treatment options, and recurrence pattern of this rare malignancy. CASE PRESENTATION We present a case of penile leiomyosarcoma in a 70-year-old patient who presented to the urology clinic with 1-year history of a slowly enlarging penile mass associated with phimosis. CONCLUSIONS Prognosis of penile LMS is difficult to ascertain because reported cases are rare. Penile leiomyosarcoma can be classified as superficial or deep based on tumor relation to tunica albuginea. Deep tumors (> 3 cm), high-grade lesions, and tumors with involvement of corpora cavernosa, tend to spread locally and metastasize to distant areas and require more radical surgery with or without postoperative radiation therapy. In contrast, superficial lesions can be treated with local excision only.
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Affiliation(s)
| | | | | | - Lezah McCarthy
- Stratton Veterans Affairs Medical Center, Albany, New York
| | | | - Syed Mehdi
- Stratton Veterans Affairs Medical Center, Albany, New York
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Aboushanab SA, Shevyrin VA, Slesarev GP, Melekhin VV, Shcheglova AV, Makeev OG, Kovaleva EG, Kim KH. Antioxidant and Cytotoxic Activities of Kudzu Roots and Soy Molasses against Pediatric Tumors and Phytochemical Analysis of Isoflavones Using HPLC-DAD-ESI-HRMS. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11060741. [PMID: 35336625 PMCID: PMC8955742 DOI: 10.3390/plants11060741] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/07/2022] [Accepted: 03/07/2022] [Indexed: 05/08/2023]
Abstract
Pediatric solid tumors (PSTs) are life-threatening and can lead to high morbidity and mortality rates in children. Developing novel remedies to treat these tumors, such as glioblastoma multiforme and sarcomas, such as osteosarcoma, and rhabdomyosarcoma, is challenging, despite immense attempts with chemotherapeutic or radiotherapeutic interventions. Soy (Glycine max) and kudzu roots (KR) (Pueraria spp.) are well-known phytoestrogenic botanical sources that contain high amounts of naturally occurring isoflavones. In the present study, we investigated the antioxidant and cytotoxic effects of the extracts of KR and soy molasses (SM) against PSTs. The green extraction of isoflavones from KR and SM was performed using natural deep eutectic solvents. The extracts were subsequently analyzed by high-performance liquid chromatography (HPLC)-diode array detector (DAD) coupled with high-resolution (HR) mass spectrometry (MS), which identified 10 isoflavones in KR extracts and 3 isoflavones in the SM extracts. Antioxidant and cytotoxic activities of KR and SM extracts were assessed against glioblastoma multiforme (A-172), osteosarcoma (HOS), and rhabdomyosarcoma (Rd) cancer cell lines. The KR and SM extracts showed satisfactory cytotoxic effects (IC50) against the cancer cell lines tested, particularly against Rd cancer cell lines, in a dose-dependent manner. Antioxidant activity was found to be significantly (p ≤ 0.05) higher in KR than in SM, which was consistent with the results of the cytotoxic activity observed with KR and SM extracts against glioblastoma and osteosarcoma cells. The total flavonoid content and antioxidant activities of the extracts were remarkably attributed to the isoflavone content in the KR and SM extracts. This study provides experimental evidence that HPLC-ESI-HRMS is a suitable analytical approach to identify isoflavones that exhibit potent antioxidant and anticancer potential against tumor cells, and that KR and SM, containing many isoflavones, can be a potential alternative for health care in the food and pharmaceutical industries.
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Affiliation(s)
- Saied A Aboushanab
- Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
- Innovative Center of Chemical and Pharmaceutical Technologies, Laboratory of Organic Synthesis, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
| | - Vadim A Shevyrin
- Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
- Innovative Center of Chemical and Pharmaceutical Technologies, Laboratory of Organic Synthesis, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
| | - Grigory P Slesarev
- Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
- Innovative Center of Chemical and Pharmaceutical Technologies, Laboratory of Organic Synthesis, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
| | - Vsevolod V Melekhin
- Innovative Center of Chemical and Pharmaceutical Technologies, Laboratory of Organic Synthesis, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
- Department of Biology, Ural State Medical University, Repina 3, 620014 Yekaterinburg, Russia
- Department of Gene and Cell Therapy, Institute for Medical Cell Technologies, Karla Marksa 22a, 620026 Yekaterinburg, Russia
| | - Anna V Shcheglova
- Innovative Center of Chemical and Pharmaceutical Technologies, Laboratory of Organic Synthesis, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
- Department of Biology, Ural State Medical University, Repina 3, 620014 Yekaterinburg, Russia
| | - Oleg G Makeev
- Department of Biology, Ural State Medical University, Repina 3, 620014 Yekaterinburg, Russia
- Department of Gene and Cell Therapy, Institute for Medical Cell Technologies, Karla Marksa 22a, 620026 Yekaterinburg, Russia
| | - Elena G Kovaleva
- Institute of Chemical Engineering, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
- Innovative Center of Chemical and Pharmaceutical Technologies, Laboratory of Organic Synthesis, Ural Federal University Named after the First President of Russia B. N. Yeltsin, Mira 19, 620002 Yekaterinburg, Russia
| | - Ki Hyun Kim
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
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Hanrahan CJ. Editorial for "Magnetic Resonance Imaging-Based Radiomics Nomogram for Prediction of the Histopathological Grade of Soft Tissue Sarcomas: A Two-Center Study". J Magn Reson Imaging 2021; 53:1697-1698. [PMID: 33713499 DOI: 10.1002/jmri.27598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 02/27/2021] [Indexed: 11/09/2022] Open
Affiliation(s)
- Christopher J Hanrahan
- Intermountain Healthcare and University of Utah School of Medicine, Salt Lake City, Utah, USA
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Yan R, Hao D, Li J, Liu J, Hou F, Chen H, Duan L, Huang C, Wang H, Yu T. Magnetic Resonance Imaging-Based Radiomics Nomogram for Prediction of the Histopathological Grade of Soft Tissue Sarcomas: A Two-Center Study. J Magn Reson Imaging 2021; 53:1683-1696. [PMID: 33604955 DOI: 10.1002/jmri.27532] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/13/2021] [Accepted: 01/15/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Preoperative prediction of soft tissue sarcoma (STS) grade is important for treatment decisions. Therefore, formulation an STS grade model is strongly needed. PURPOSE To develop and test an magnetic resonance imaging (MRI)-based radiomics nomogram for predicting the grade of STS (low-grade vs. high grade). STUDY TYPE Retrospective POPULATION: One hundred and eighty patients with STS confirmed by pathologic results at two independent institutions were enrolled (training set, N = 109; external validation set, N = 71). FIELD STRENGTH/SEQUENCE Unenhanced T1-weighted (T1WI) and fat-suppressed T2-weighted images (FS-T2WI) were acquired at 1.5 T and 3.0 T. ASSESSMENT Clinical-MRI characteristics included age, gender, tumor-node-metastasis (TNM) stage, American Joint Committee on Cancer (AJCC) stage, progression-free survival (PFS), and MRI morphological features (ie, margin). Radiomics feature extraction were performed on T1WI and FS-T2WI images by minimum redundancy maximum relevance (MRMR) method and least absolute shrinkage and selection operator (LASSO) algorithm. The selected features constructed three radiomics signatures models (RS-T1， RS-FST2, and RS-Combined). Univariate and multivariate logistic regression analysis were applied for screening significant risk factors. Radiomics nomogram was constructed by incorporating the radiomics signature and risk factors. STATISTICAL TESTS Clinical-MRI characteristics were performed by a univariate analysis. Model performances (discrimination, calibration, and clinical usefulness) were validated in the external validation set. The RS-T1 model, RS-FST2 model, and RS-Combined model had an area under curves (AUCs) of 0.645, 0.641, and 0.829, respectively, in the external validation set. The radiomics nomogram, incorporating significant risk factors and the RS-Combined model had AUCs of 0.916 (95%CI, 0.866-0.966, training set) and 0.879 (95%CI, 0.791-0.967, external validation set), and demonstrated good calibration and good clinical utility. DATA CONCLUSION The proposed noninvasive MRI-based radiomics models showed good performance in differentiating low-grade from high-grade STSs. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY STAGE: 2.
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Affiliation(s)
- Ruixin Yan
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Dapeng Hao
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Jie Li
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Jihua Liu
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Feng Hou
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Haisong Chen
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Lisha Duan
- Department of CT/MRI, The Third Hospital of Hebei Medical University, Shi jiazhuang, Hebei, 050051, China
| | - Chencui Huang
- Department of Research Collaboration, R&D center, Beijing Deepwise & League of PHD Technology Co., Ltd, Beijing, 100080, China
| | - Hexiang Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, China
| | - Tengbo Yu
- Department of Sports Medicine, the Affiliated Hospital of Qingdao University, QingDao, Shandong, 266003, China
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Grünewald TGP, Alonso M, Avnet S, Banito A, Burdach S, Cidre‐Aranaz F, Di Pompo G, Distel M, Dorado‐Garcia H, Garcia‐Castro J, González‐González L, Grigoriadis AE, Kasan M, Koelsche C, Krumbholz M, Lecanda F, Lemma S, Longo DL, Madrigal‐Esquivel C, Morales‐Molina Á, Musa J, Ohmura S, Ory B, Pereira‐Silva M, Perut F, Rodriguez R, Seeling C, Al Shaaili N, Shaabani S, Shiavone K, Sinha S, Tomazou EM, Trautmann M, Vela M, Versleijen‐Jonkers YMH, Visgauss J, Zalacain M, Schober SJ, Lissat A, English WR, Baldini N, Heymann D. Sarcoma treatment in the era of molecular medicine. EMBO Mol Med 2020; 12:e11131. [PMID: 33047515 PMCID: PMC7645378 DOI: 10.15252/emmm.201911131] [Citation(s) in RCA: 163] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 07/20/2020] [Accepted: 07/24/2020] [Indexed: 12/14/2022] Open
Abstract
Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.
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Affiliation(s)
- Thomas GP Grünewald
- Max‐Eder Research Group for Pediatric Sarcoma BiologyInstitute of PathologyFaculty of MedicineLMU MunichMunichGermany
- Division of Translational Pediatric Sarcoma ResearchGerman Cancer Research Center (DKFZ), Hopp Children's Cancer Center (KiTZ), German Cancer Consortium (DKTK)HeidelbergGermany
- Institute of PathologyHeidelberg University HospitalHeidelbergGermany
| | - Marta Alonso
- Program in Solid Tumors and BiomarkersFoundation for the Applied Medical ResearchUniversity of Navarra PamplonaPamplonaSpain
| | - Sofia Avnet
- Orthopedic Pathophysiology and Regenerative Medicine UnitIRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Ana Banito
- Pediatric Soft Tissue Sarcoma Research GroupGerman Cancer Research Center (DKFZ)HeidelbergGermany
| | - Stefan Burdach
- Department of Pediatrics and Children's Cancer Research Center (CCRC)Technische Universität MünchenMunichGermany
| | - Florencia Cidre‐Aranaz
- Max‐Eder Research Group for Pediatric Sarcoma BiologyInstitute of PathologyFaculty of MedicineLMU MunichMunichGermany
| | - Gemma Di Pompo
- Orthopedic Pathophysiology and Regenerative Medicine UnitIRCCS Istituto Ortopedico RizzoliBolognaItaly
| | | | | | | | | | | | - Merve Kasan
- Max‐Eder Research Group for Pediatric Sarcoma BiologyInstitute of PathologyFaculty of MedicineLMU MunichMunichGermany
| | | | | | - Fernando Lecanda
- Division of OncologyAdhesion and Metastasis LaboratoryCenter for Applied Medical ResearchUniversity of NavarraPamplonaSpain
| | - Silvia Lemma
- Orthopedic Pathophysiology and Regenerative Medicine UnitIRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Dario L Longo
- Institute of Biostructures and Bioimaging (IBB)Italian National Research Council (CNR)TurinItaly
| | | | | | - Julian Musa
- Max‐Eder Research Group for Pediatric Sarcoma BiologyInstitute of PathologyFaculty of MedicineLMU MunichMunichGermany
- Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany
| | - Shunya Ohmura
- Max‐Eder Research Group for Pediatric Sarcoma BiologyInstitute of PathologyFaculty of MedicineLMU MunichMunichGermany
| | | | - Miguel Pereira‐Silva
- Department of Pharmaceutical TechnologyFaculty of PharmacyUniversity of CoimbraCoimbraPortugal
| | - Francesca Perut
- Orthopedic Pathophysiology and Regenerative Medicine UnitIRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Rene Rodriguez
- Instituto de Investigación Sanitaria del Principado de AsturiasOviedoSpain
- CIBER en oncología (CIBERONC)MadridSpain
| | | | - Nada Al Shaaili
- Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
| | - Shabnam Shaabani
- Department of Drug DesignUniversity of GroningenGroningenThe Netherlands
| | - Kristina Shiavone
- Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
| | - Snehadri Sinha
- Department of Oral and Maxillofacial DiseasesUniversity of HelsinkiHelsinkiFinland
| | | | - Marcel Trautmann
- Division of Translational PathologyGerhard‐Domagk‐Institute of PathologyMünster University HospitalMünsterGermany
| | - Maria Vela
- Hospital La Paz Institute for Health Research (IdiPAZ)MadridSpain
| | | | | | - Marta Zalacain
- Institute of Biostructures and Bioimaging (IBB)Italian National Research Council (CNR)TurinItaly
| | - Sebastian J Schober
- Department of Pediatrics and Children's Cancer Research Center (CCRC)Technische Universität MünchenMunichGermany
| | - Andrej Lissat
- University Children′s Hospital Zurich – Eleonoren FoundationKanton ZürichZürichSwitzerland
| | - William R English
- Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
| | - Nicola Baldini
- Orthopedic Pathophysiology and Regenerative Medicine UnitIRCCS Istituto Ortopedico RizzoliBolognaItaly
- Department of Biomedical and Neuromotor SciencesUniversity of BolognaBolognaItaly
| | - Dominique Heymann
- Department of Oncology and MetabolismUniversity of SheffieldSheffieldUK
- Université de NantesInstitut de Cancérologie de l'OuestTumor Heterogeneity and Precision MedicineSaint‐HerblainFrance
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Wang Z, Zhang S, Yang H, Zhuang R, Guo X, Tong H, Zhang Y, Lu W, Zhou Y. Efficacy and safety of anlotinib, a multikinase angiogenesis inhibitor, in combination with epirubicin in preclinical models of soft tissue sarcoma. Cancer Med 2020; 9:3344-3352. [PMID: 32181596 PMCID: PMC7221313 DOI: 10.1002/cam4.2941] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 01/05/2020] [Accepted: 01/31/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Anlotinib is a novel, orally administered, multitarget receptor tyrosine kinase inhibitor. It functions by inhibiting tumor angiogenesis and proliferative signaling pathways. In this study, we aimed to investigate the efficacy and safety of anlotinib plus epirubicin in a sarcoma patient-derived xenografts (PDX) model. METHODS We firstly established a PDX model using fresh tumor tissues that were surgically removed from a patient diagnosed with malignant fibrous histiocytoma. Thirty-six PDX models were divided into six groups and treated with anlotinib alone (low-dose, 1.5 or high-dose, 3.0 mg/kg/day, oral gavage), or with anlotinib plus epirubicin (3.0 mg/kg/once weekly, i.p.) when the tumors grew to 150-200 mm3 . After 5 weeks of treatment, the mice were sacrificed, and the tumors were measured by weight and processed for IHC and H&E staining. IHC staining was performed to detect CD31, EGFR, MVD, and Ki-67 on paraffin sections. H&E stainings were performed to examine the microcosmic changes that occurred in the tumor tissues and myocardium, respectively. RESULTS After 5 weeks, treatment with anlotinib or epirubicin alone significantly inhibited tumor growth in the sarcoma PDX model compared with the vehicle control. Tumor volume in the high-dose anlotinib group was significantly smaller than the low-dose anlotinib group (P < .001). Combined high-dose anlotinib and epirubicin treatment resulted in the most pronounced tumor inhibition. In the groups treated with the anlotinib-containing regimen, the expression levels of CD31, EGFR, MVD, and Ki-67 were significantly low. The weight in each group had no statistical differences; the same applied to the hepatic function, cardiac function, and toxicity. CONCLUSIONS High-dose anlotinib combined with epirubicin was an effective and safe therapy for STS.
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Affiliation(s)
- Zhi‐Ming Wang
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghaiChina
- Xiamen BranchZhongshan HospitalFudan UniversityXiamenChina
| | - Shi‐Long Zhang
- Minhang HospitalFudan UniversityShanghaiChina
- Minhang HospitalFudan UniversityInstitute of Fudan‐Minhang Academic Health SystemShanghaiChina
| | - Hua Yang
- Department of General SurgeryShanghai Public Health Clinical CenterZhongshan Hospital (South Branch)Fudan UniversityShanghaiChina
| | - Rong‐Yuan Zhuang
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghaiChina
| | - Xi Guo
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghaiChina
| | - Han‐Xing Tong
- Department of General SurgeryShanghai Public Health Clinical CenterZhongshan Hospital (South Branch)Fudan UniversityShanghaiChina
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Yong Zhang
- Department of General SurgeryShanghai Public Health Clinical CenterZhongshan Hospital (South Branch)Fudan UniversityShanghaiChina
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Wei‐Qi Lu
- Department of General SurgeryShanghai Public Health Clinical CenterZhongshan Hospital (South Branch)Fudan UniversityShanghaiChina
- Department of General SurgeryZhongshan HospitalFudan UniversityShanghaiChina
| | - Yu‐Hong Zhou
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghaiChina
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10
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Gómez J, Tsagozis P. Multidisciplinary treatment of soft tissue sarcomas: An update. World J Clin Oncol 2020; 11:180-189. [PMID: 32355640 PMCID: PMC7186235 DOI: 10.5306/wjco.v11.i4.180] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/13/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Standard treatment for soft tissue sarcoma, based on complete surgical resection with or without adjuvant radiotherapy and chemotherapy, has not substantially changed during the last several decades. Nevertheless, recent advances have contributed to considerable improvement in the management of these patients; for example, new magnetic resonance imaging sequences such as diffusion-weighted imaging and magnetic resonance imaging radiomics can better assess tumor extension and even estimate its grade. Detection of circulating genetic material (liquid biopsy) and next-generation sequencing are powerful techniques for genetic analysis, which will increase our understanding of the underlying molecular mechanisms and may reveal potential therapeutic targets. The role of chemotherapy in non-metastatic disease is still controversial, and there is a need to identify patients who really benefit from this treatment. Novel chemotherapeutic regimens have entered clinical praxis and can change the outcome of patients with metastatic disease. Advances in radiotherapy have helped decrease local adverse effects and sustain good local control of the disease. The following report provides an updated view of the diagnosis, treatment, and future perspectives on the management of patients with soft tissue sarcomas.
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Affiliation(s)
- Jorge Gómez
- Department of Orthopedic Surgery, Clínica Universidad de Navarra, University of Navarra, Pamplona 31008, Spain
| | - Panagiotis Tsagozis
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm 17176, Sweden
- Muskuloskeletal Tumour Service, Karolinska University Hospital, Stockholm 17176, Sweden
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11
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Borgatti A, Dickerson EB, Lawrence J. Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional. Vet Comp Oncol 2019; 18:9-24. [PMID: 31749286 DOI: 10.1111/vco.12554] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 11/08/2019] [Accepted: 11/11/2019] [Indexed: 12/21/2022]
Abstract
Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low-grade sarcomas and remains the standard therapeutic approach. For advanced, high-grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches. The discovery of "Coley's toxins" in the 19th century, and their use to stimulate the immune system supported the application of unconventional therapies for the treatment of sarcomas. While promising, this initial work was abandoned and treatment paradigm and disease course of sarcomas was largely unchanged for several decades. Exciting new therapies are currently changing treatment algorithms for advanced carcinomas and melanomas, and similar approaches are being applied to advance the field of sarcoma research. Recent discoveries in subtype-specific cancer biology and the identification of distinct molecular targets have led to the development of promising targeted strategies with remarkable potential to change the landscape of sarcoma therapy in dogs. The purpose of this review article is to describe the current standard of care and limitations as well as emerging approaches for sarcoma therapy that span many of the most active paradigms in oncologic research, including immunotherapies, checkpoint inhibitors, and drugs capable of cellular metabolic reprogramming.
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Affiliation(s)
- Antonella Borgatti
- Animal Cancer Care and Research (ACCR) Program, University of Minnesota, St. Paul, Minnesota.,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota.,Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.,Clinical Investigation Center, College of Veterinary Medicine, St. Paul, Minnesota
| | - Erin B Dickerson
- Animal Cancer Care and Research (ACCR) Program, University of Minnesota, St. Paul, Minnesota.,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota.,Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
| | - Jessica Lawrence
- Animal Cancer Care and Research (ACCR) Program, University of Minnesota, St. Paul, Minnesota.,Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota.,Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
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12
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Jiang S, Yang Y, Mo C, Chen L, Qiu S, Huang B, Chen J. Localized giant solitary fibrous tumor of the scrotum: a rare case report and literature review. J Int Med Res 2019; 47:5802-5808. [PMID: 31452410 PMCID: PMC6862882 DOI: 10.1177/0300060519869140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background A solitary fibrous tumor (SFT) is a fibroblastic mesenchymal tumor initially thought to originate from the pleura but that may arise at almost any anatomic site. It is mostly benign, and surgical resection is usually the best treatment option. An SFT involving the scrotum is extremely rare. Case presentation: We herein report an uncommon case of a 22-year-old man who presented with a huge asymptomatic scrotal mass that had begun growing 3 years before presentation. Contrast-enhanced computed tomography revealed a heterogeneous, well-circumscribed scrotal mass with soft tissue density. No invasion of the surrounding organs, distal metastasis, or lymph node swelling was present. Complete resection of the mass was successfully performed. The specimen was a 14.5 × 12.0 × 9.5 cm encapsulated tumor that weighed 970 g. After pathological analysis, we confirmed the diagnosis of SFT. This diagnosis was based on clinical findings, histological morphology, and immunohistochemistry. No recurrence or metastasis was observed during a 3-year follow-up. Conclusion SFTs have an unpredictable clinical course, and they are difficult to diagnose and easy to misdiagnose. A scrotal location is extremely rare. Complete resection of the mass is the treatment of choice and is associated with a high success rate and low recurrence rate.
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Affiliation(s)
- Shuangjian Jiang
- Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yun Yang
- Department of Anesthesia Surgery Center, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Chengqiang Mo
- Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Lingwu Chen
- Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Shaopeng Qiu
- Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Bin Huang
- Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Junxing Chen
- Department of Urology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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13
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Das B, Roy J, Jain N, Mallick B. Tumor suppressive activity of PIWI-interacting RNA in human fibrosarcoma mediated through repression of RRM2. Mol Carcinog 2018; 58:344-357. [DOI: 10.1002/mc.22932] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 10/23/2018] [Accepted: 10/23/2018] [Indexed: 12/30/2022]
Affiliation(s)
- Basudeb Das
- RNAi and Functional Genomics Lab; Department of Life Science; National Institute of Technology; Rourkela Odisha India
| | - Jyoti Roy
- RNAi and Functional Genomics Lab; Department of Life Science; National Institute of Technology; Rourkela Odisha India
| | - Neha Jain
- RNAi and Functional Genomics Lab; Department of Life Science; National Institute of Technology; Rourkela Odisha India
| | - Bibekanand Mallick
- RNAi and Functional Genomics Lab; Department of Life Science; National Institute of Technology; Rourkela Odisha India
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14
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Xu J, Du Y, Liu WJ, Li L, Li Y, Wang XF, Yi HF, Shan CK, Xia GM, Liu XJ, Zhen YS. Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity. Drug Deliv 2018; 25:102-111. [PMID: 29250984 PMCID: PMC6058573 DOI: 10.1080/10717544.2017.1410261] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas. In addition, tissue inhibitor of metalloproteinase 2 (TIMP2) displays specific interaction with MMPs. Therefore, TIMP2 may play an active role in the development of fibrosarcoma-targeting agents. In the current study, a TIMP2-based recombinant protein LT and its enediyne-integrated analog LTE were prepared; furthermore, the fibrosarcoma-binding intensity and antitumor activity were investigated. As shown, intense and selective binding capability of the protein LT to human fibrosarcoma specimens was confirmed by tissue microarray. Moreover, LTE, the enediyne-integrated analog of LT, exerted highly potent cytotoxicity to fibrosarcoma HT1080 cells, induced apoptosis, and caused G2/M arrest. LTE at 0.1 nM markedly suppressed the migration and invasion of HT1080 cells. LTE at tolerated dose of 0.6 mg/kg inhibited the tumor growth of fibrosarcoma xenograft in athymic mice. The study provides evidence that the TIMP2-based reconstituted analog LTE may be useful as a targeted drug for fibrosarcome therapy.
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Affiliation(s)
- Jian Xu
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Yue Du
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Wen-Juan Liu
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.,b Shandong Provincial Key Laboratory of Radiation Oncology , Shandong Cancer Hospital and Institute, Shandong Cancer Hospital affiliated to Shandong University Shandong Academy of Medical Sciences , Jinan , China
| | - Liang Li
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Yi Li
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Xiao-Fei Wang
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Hong-Fei Yi
- c West China Hospital, Sichuan University and Collaborative Innovation Center , Chengdu , China
| | - Chuan-Kun Shan
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Gui-Min Xia
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Xiu-Jun Liu
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
| | - Yong-Su Zhen
- a Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
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15
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Montgomery C, Harris J, Siegel E, Suva L, Wilson M, Morell S, Nicholas R. Obesity is associated with larger soft-tissue sarcomas, more surgical complications, and more complex wound closures (obesity leads to larger soft-tissue sarcomas). J Surg Oncol 2018; 118:184-191. [PMID: 29878365 DOI: 10.1002/jso.25119] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 05/07/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES Does a link exist between obesity and soft-tissue sarcoma outcomes? We hypothesized that soft-tissue sarcomas in patients with obesity may lead to larger tumors at detection, with an increased risk for a more complex surgical excision, wound healing-related complications, higher stage at presentation, and decreased survival. METHODS One hundred thirty-nine and patients with soft-tissue sarcoma were retrospectively evaluated over 10 years. Patients were divided into 2 cohorts based on the World Health Organization body mass index (BMI) obesity grouping. A BMI ≥ 30 kg/m2 was classified as obese and a BMI < 30 kg/m2 was classified as nonobese. RESULTS Eighty-five nonobese and 54 obese individuals were evaluated. The median tumor diameter was 50% larger (P = .024) and the overall complication rate was 1.7-fold higher in patients with obesity (P = .0032). Patients with obesity also had a statistically significantly higher rate of complex wound closures. In multivariable logistic regression, obesity remained a highly significant factor favoring complications after the surgical treatment of soft-tissue sarcoma (odds ratio = 3.66, 95% confidence interval = 1.54-8.71; P = .0033). No statistically significant differences were noted on comparing groups for the incidence of metastatic spread or survival. CONCLUSIONS These findings suggest that obesity is associated with larger tumors, a higher incidence of wound complications, and greater use of complex wound-closure methods.
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Affiliation(s)
- Corey Montgomery
- Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - John Harris
- Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Eric Siegel
- Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Larry Suva
- Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas
| | - Margaret Wilson
- Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Sean Morell
- Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas
| | - Richard Nicholas
- Department of Orthopaedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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16
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Heitkötter B, Trautmann M, Grünewald I, Bögemann M, Rahbar K, Gevensleben H, Wardelmann E, Hartmann W, Steinestel K, Huss S. Expression of PSMA in tumor neovasculature of high grade sarcomas including synovial sarcoma, rhabdomyosarcoma, undifferentiated sarcoma and MPNST. Oncotarget 2018; 8:4268-4276. [PMID: 28002805 PMCID: PMC5354830 DOI: 10.18632/oncotarget.13994] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Accepted: 11/30/2016] [Indexed: 11/25/2022] Open
Abstract
AIMS PSMA (prostate specific membrane antigen) is physiologically expressed in normal prostate tissue. It is overexpressed in prostate cancer cells and has been suggested as a target for antibody-based radioligand therapy. As PSMA expression so far has not been systematically analyzed in soft tissue tumors, the current study aims at investigating a large cohort of different subtypes. METHODS AND RESULTS Immunohistochemistry was used to detect PSMA expression in 779 samples of soft tissue tumors and Ewing sarcoma as a primary bone malignancy. CD34 coexpression was employed to study PSMA expression in the neovasculature. PSMA expression was found in the tumor-associated neovasculature of 151/779 soft tissue/bone tumors (19.38%) and was more frequent in malignant tumors compared to tumors with intermediate or benign biological potential (p=0.078). Strong neovascular PSMA expression was predominantly observed in subsets of different sarcomas including 3/20 rhabdomyosarcomas (15%), 4/21 malignant peripheral nerve sheath tumors (19.05%), 6/16 synovial sarcomas (35.29%) and 6/33 undifferentiated pleomorphic sarcomas (18.18%). CONCLUSION We conclude that PSMA is expressed in the neovasculature of a subset of soft tissue tumors to a variable extent. Our observation of strong PSMA expression predominantly occurring in sarcomas might provide a rationale to evaluate PSMA-targeted radioligand therapy in these entities.
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Affiliation(s)
- Birthe Heitkötter
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
| | - Marcel Trautmann
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
| | - Inga Grünewald
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
| | - Martin Bögemann
- Department of Urology, University Hospital Münster, University of Münster, Germany
| | - Kambiz Rahbar
- Department of Nuclear Medicine, University Hospital Münster, University of Münster, Germany
| | - Heidrun Gevensleben
- Institute of Pathology, University Hospital Bonn, University of Bonn, Germany
| | - Eva Wardelmann
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
| | - Wolfgang Hartmann
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
| | - Konrad Steinestel
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
| | - Sebastian Huss
- Gerhard Domagk Institute of Pathology, University Hospital Münster, University of Münster, Germany
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17
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Broecker JS, Ethun CG, Monson DK, Lopez-Aguiar AG, Le N, McInnis M, Godette K, Reimer NB, Oskouei SV, Delman KA, Staley CA, Maithel SK, Cardona K. The Oncologic Impact of Postoperative Complications Following Resection of Truncal and Extremity Soft Tissue Sarcomas. Ann Surg Oncol 2017; 24:3574-3586. [DOI: 10.1245/s10434-017-6034-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Indexed: 12/28/2022]
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18
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Sellevold S, Peng Q, Fremstedal ASV, Berg K. Photochemical internalization (PCI) of bleomycin is equally effective in two dissimilar leiomyosarcoma xenografts in athymic mice. Photodiagnosis Photodyn Ther 2017; 20:95-106. [PMID: 28865875 DOI: 10.1016/j.pdpdt.2017.08.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 08/21/2017] [Accepted: 08/27/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Photochemical internalization (PCI) is a novel technique for delivery of active macromolecules into cancerous cells, via light activation of a specific photosensitizer and a low dose systemic drug. Numerous pre-clinical studies and one clinical trial have confirmed the treatment potential in carcinomas. Soft tissue sarcomas are rare and generally resistant to radio- and chemotherapy. Due to treatment resistance and surgical morbidity in sarcoma care, we seek to increase knowledge on PCI effects in sarcomas by studying two different, but closely related leiomyosarcomas. METHODS MES-SA and SK-LMS-1 tumours were established in the leg muscles of athymic mice. Treatment effects after AlPcS2a-PCI of bleomycin, PCI with no drug (photodynamic therapy, PDT) and control groups were evaluated by: 1) assessment of tumour growth, 2) uptake of contrast agent during MRI and 3) histopathology. RESULTS PCI of bleomycin induced a similar and significant increase in time to reach the end point in both tumour models, while neither responded to AlPcS2a-PDT. In the MES-SA tumours PCI reduced the growth rate, while in the SK-LMS-1 tumours the growth was blocked for 12days followed by exponential growth close to that of untreated tumours. SK-LMS-1 tumours were more homogenously and better vascularized than MES-SA. After PCI the vascular shutdown was more complete in the SK-LMS-1 tumours than in the MES-SA tumours. CONCLUSIONS AlPcS2a-based PCI, but not PDT, induced significant tumour growth delay in the evaluated sarcomas. Cellular responsiveness to bleomycin and tumour vascularity are identified as predictive markers for PCI treatment effects.
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Affiliation(s)
- Simen Sellevold
- Division of Orthopaedic Surgery, Oslo University Hospital, Norway; Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
| | - Qian Peng
- Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Norway
| | - Ane Sofie Viset Fremstedal
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway
| | - Kristian Berg
- Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway.
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19
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Zhou Y, Chu X, Yi Y, Tong L, Dai Y. Malignant solitary fibrous tumor in retroperitoneum: A case report and literature review. Medicine (Baltimore) 2017; 96:e6373. [PMID: 28296778 PMCID: PMC5369933 DOI: 10.1097/md.0000000000006373] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
RATIONALE Solitary fibrous tumor (SFT) is a rare mesenchymal tumor occurs in various sites. Malignant SFT in retroperitoneum is extremely rare. PATIENT CONCERNS We report a case of malignant retroperitoneal SFT in a 59-year-old man presented with right flank pain for 1 month. DIAGNOSES, INTERVENTIONS AND OUTCOMES A laparotomy and resection of the tumor were performed, the histopathologic and immunohistochemical findings were consistent with malignant retroperitoneal SFT. No adjuvant treatment was performed, and the patient had no signs of recurrence or metastasis at the 12 months follow-up. LESSONS Complete surgical excision is the basic treatment principle for malignant retroperitoneal SFT. The histologic features and the Ki-67 label index are helpful for the diagnosis of malignant SFT.
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20
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Harati K, Behr B, Daigeler A, Hirsch T, Jacobsen F, Renner M, Harati A, Wallner C, Lehnhardt M, Becerikli M. Curcumin and Viscum album Extract Decrease Proliferation and Cell Viability of Soft-Tissue Sarcoma Cells: An In Vitro Analysis of Eight Cell Lines Using Real-Time Monitoring and Colorimetric Assays. Nutr Cancer 2017; 69:340-351. [PMID: 28045549 DOI: 10.1080/01635581.2017.1263349] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The cytostatic effects of the polyphenol curcumin and Viscum album extract (VAE) were assessed in soft-tissue sarcoma (STS) cells. METHODS Eight human STS cell lines were used: fibrosarcoma (HT1080), liposarcoma (SW872, T778, MLS-402), synovial sarcoma (SW982, SYO1, 1273), and malignant fibrous histiocytoma (U2197). Primary human fibroblasts served as control cells. Cell proliferation, viability, and cell index (CI) were analyzed by BrdU assay, MTT assay, and real-time cell analysis (RTCA). RESULTS As indicated by BrdU and MTT, curcumin significantly decreased the cell proliferation of five cell lines (HT1080, SW872, SYO1, 1273, and U2197) and the viability of two cell lines (SW872 and SW982). VAE led to significant decreases of proliferation in eight cell lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, 1293, and U2197) and reduced viability in seven STS lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, and 1273). As indicated by RTCA for 160 h, curcumin decreased the CI of all synovial sarcoma cell lines as well as T778 and HT1080. VAE diminished the CI in most of the synovial sarcoma (SW982, SYO1) and liposarcoma (SW872, T778) cell lines as well as HT1080. Primary fibroblasts were not affected adversely by the two compounds in RTCA. CONCLUSION Curcumin and VAE can inhibit the proliferation and viability of STS cells.
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Affiliation(s)
- K Harati
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - B Behr
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - A Daigeler
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - T Hirsch
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - F Jacobsen
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - M Renner
- b Institute of Pathology, University of Heidelberg , Heidelberg , Germany
| | - A Harati
- c Department of Neurosurgery , Klinikum Dortmund , Dortmund , Germany
| | - C Wallner
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - M Lehnhardt
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
| | - M Becerikli
- a Department of Plastic Surgery , Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil Bochum , Bochum , Germany
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21
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Harati K, Behr B, Wallner C, Daigeler A, Hirsch T, Jacobsen F, Renner M, Harati A, Lehnhardt M, Becerikli M. Anti‑proliferative activity of epigallocatechin‑3‑gallate and silibinin on soft tissue sarcoma cells. Mol Med Rep 2016; 15:103-110. [PMID: 27909727 PMCID: PMC5355719 DOI: 10.3892/mmr.2016.5969] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 10/26/2016] [Indexed: 12/17/2022] Open
Abstract
Disseminated soft tissue sarcomas (STS) present a therapeutic dilemma. The first-line cytostatic doxorubicin demonstrates a response rate of 30% and is not suitable for elderly patients with underlying cardiac disease, due to its cardiotoxicity. Well‑tolerated alternative treatment options, particularly in palliative situations, are rare. Therefore, the present study assessed the anti‑proliferative effects of the natural compounds epigallocatechin-3-gallate (EGCG), silibinin and noscapine on STS cells. A total of eight different human STS cell lines were used in the study: Fibrosarcoma (HT1080), liposarcoma (SW872, T778 and MLS‑402), synovial sarcoma (SW982, SYO1 and 1273) and pleomorphic sarcoma (U2197). Cell proliferation and viability were analysed by 5‑bromo-2'-deoxyuridine and MTT assays and real‑time cell analysis (RTCA). RTCA indicated that noscapine did not exhibit any inhibitory effects. By contrast, EGCG decreased proliferation and viability of all cell lines except for the 1273 synovial sarcoma cell line. Silibinin exhibited anti‑proliferative effects on all synovial sarcoma, liposarcoma and fibrosarcoma cell lines. Liposarcoma cell lines responded particularly well to EGCG while synovial sarcoma cell lines were more sensitive to silibinin. In conclusion, the green tea polyphenol EGCG and the natural flavonoid silibinin from milk thistle suppressed the proliferation and viability of liposarcoma, synovial sarcoma and fibrosarcoma cells. These compounds are therefore potential candidates as mild therapeutic options for patients that are not suitable for doxorubicin‑based chemotherapy and require palliative treatment. The findings from the present study provide evidence to support in vivo trials assessing the effect of these natural compounds on solid sarcomas.
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Affiliation(s)
- Kamran Harati
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Björn Behr
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Christoph Wallner
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Adrien Daigeler
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Tobias Hirsch
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Frank Jacobsen
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Marcus Renner
- Institute of Pathology, University of Heidelberg, D‑69120 Heidelberg, Germany
| | - Ali Harati
- Department of Neurosurgery, Klinikum Dortmund, D‑44145 Dortmund, Germany
| | - Marcus Lehnhardt
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
| | - Mustafa Becerikli
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, D‑44789 Bochum, Germany
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Bray JP. Soft tissue sarcoma in the dog - part 1: a current review. J Small Anim Pract 2016; 57:510-519. [PMID: 27624929 DOI: 10.1111/jsap.12556] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 07/07/2016] [Accepted: 08/08/2016] [Indexed: 12/24/2022]
Abstract
Soft tissue sarcomas are derived from tissues of mesenchymal origin. Although local recurrence following surgical resection is the characteristic challenge in their management, 40% dogs with high-grade tumours may also develop metastatic disease, despite successful local control. Soft tissue sarcoma is a complex disease and there are many uncertainties regarding the biology and optimal clinical management. There are currently no diagnostic tests that can reliably predict the amount of surgical margin required for a particular tumour, so there can be a mismatch between treatment and disease. Historically, the tendency has been to always recommend wide excision margins but this is not fully supported by recent evidence. A selection bias for less aggressive soft tissue sarcomas in primary care practice can account for good outcomes that are achieved despite narrow surgical excision margins. On the other hand, inappropriately conservative treatment will adversely affect outcomes for patients with more aggressive disease. This review provides an update on the current understanding of management of canine soft tissue sarcomas.
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Affiliation(s)
- J P Bray
- Veterinary Teaching Hospital, Institute for Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North 4442, New Zealand.
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Lawrence J, Cameron D, Argyle D. Species differences in tumour responses to cancer chemotherapy. Philos Trans R Soc Lond B Biol Sci 2016; 370:rstb.2014.0233. [PMID: 26056373 DOI: 10.1098/rstb.2014.0233] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Despite advances in chemotherapy, radiotherapy and targeted drug development, cancer remains a disease of high morbidity and mortality. The treatment of human cancer patients with chemotherapy has become commonplace and accepted over the past 100 years. In recent years, and with a similar incidence of cancer to people, the use of cancer chemotherapy drugs in veterinary patients such as the dog has also become accepted clinical practice. The poor predictability of tumour responses to cancer chemotherapy drugs in rodent models means that the standard drug development pathway is costly, both in terms of money and time, leading to many drugs failing in Phase I and II clinical trials. This has led to the suggestion that naturally occurring cancers in pet dogs may offer an alternative model system to inform rational drug development in human oncology. In this review, we will explore the species variation in tumour responses to conventional chemotherapy and highlight our understanding of the differences in pharmacodynamics, pharmacokinetics and pharmacogenomics between humans and dogs. Finally, we explore the potential hurdles that need to be overcome to gain the greatest value from comparative oncology studies.
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Affiliation(s)
- Jessica Lawrence
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush EH25 9RG, UK
| | - David Cameron
- University of Edinburgh Cancer Research Centre, Western General Hospital, Edinburgh EH4 2LF, UK
| | - David Argyle
- Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush EH25 9RG, UK
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Harati K, Emmelmann S, Behr B, Goertz O, Hirsch T, Kapalschinski N, Kolbenschlag J, Stricker I, Tannapfel A, Lehnhardt M, Daigeler A. Evaluation of the safety and efficacy of TRAIL and taurolidine use on human fibrosarcoma xenografts in vivo. Oncol Lett 2016; 11:1955-1961. [PMID: 26998107 DOI: 10.3892/ol.2016.4118] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 12/16/2015] [Indexed: 01/12/2023] Open
Abstract
Fibrosarcomas are rare malignant soft tissue tumours that exhibit a poor response to current therapeutic regimens. Previously, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and taurolidine were observed to induce apoptosis synergistically in HT1080 human fibrosarcoma cells in vitro. Consequently, the present study aimed to assess the safety and efficacy of TRAIL in combination with taurolidine on the local growth of fibrosarcoma xenografts in vivo. HT1080 fibrosarcoma cells were inoculated subcutaneously into both flanks of 49 athymic nude mice in order to establish tumour xenografts. TRAIL and taurolidine were applied intraperitoneally at various single and cumulative treatment doses. After 12 days, the experiment was terminated and surviving animals were euthanised. Tumour progression was determined during and following treatment. To assess the potential toxic effects of the two compounds, the organs (lung, liver, kidney and heart) of all animals were examined histologically. The results revealed that combined treatment with TRAIL and taurolidine significantly inhibited the growth of HT1080 xenografts, whereas untreated animals had steadily increasing tumours. The most effective combination was TRAIL at 2 µg per application (cumulative dose, 16 µg) and taurolidine at 30/15 mg per application (cumulative dose, 180 mg), reducing the mean size of implanted xenografts to 10.9 mm2 following treatment (vs. 48.9 mm2 in the control group; P=0.0100). Despite distinct tumour mass reduction, the rate of mortality was significantly increased in animals treated with TRAIL and taurolidine in a taurolidine dose-dependent manner; however, histological examinations of relevant organs revealed no evidence of systemic toxicity (mean survival time, 7.9 days in the treated groups vs. 12 days in the control group; P<0.0010). In summary, whilst the combination of TRAIL and taurolidine synergistically inhibited the growth of fibrosarcoma xenografts in vivo, it was also accompanied by significantly increased mortality rate. Thus, although taurolidine is assumed to be a compound with an acceptable toxicity profile, and therefore increasingly used in clinical trials, the current findings raise concerns with regard to its safety and therapeutic index, and indicate the requirement for further detailed toxicity tests.
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Affiliation(s)
- Kamran Harati
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Sabine Emmelmann
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Björn Behr
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Ole Goertz
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Tobias Hirsch
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Nicolai Kapalschinski
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Jonas Kolbenschlag
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Ingo Stricker
- Institute of Pathology, Ruhr-University Bochum, Bochum D-44789, Germany
| | - Andrea Tannapfel
- Institute of Pathology, Ruhr-University Bochum, Bochum D-44789, Germany
| | - Marcus Lehnhardt
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
| | - Adrien Daigeler
- Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG-University Hospital Bergmannsheil, Bochum D-44789, Germany
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Abstract
We report on a large, retroperitoneal, malignant, solitary fibrous tumor (SFT) with high proliferation activity. A 43-year-old man was admitted to our department complaining of a palpable mass. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large retroperitoneal tumor occupying the entire abdominal cavity. A laparotomy was performed for diagnosis and treatment, which revealed a tumor in the retroperitoneum but with no invasion to the surrounding organs, thereby allowing safe macroscopic excision. Histologically, the tumor was composed of spindle-shaped cells with patternless pattern and a hemangiopericytomatous appearance. Moreover, immunohistochemical staining was positive for CD34, vimentin, Bcl-2, and CD99 and negative for desmin, S-100p, and smooth muscle actin (AMA). The tumor exhibited high cellularity, moderate mitotic activity, pleomorphism, necrosis, and hemorrhagic changes. In addition, the Ki-67 labeling index was 37%. These findings confirmed the diagnosis of malignant SFT with high proliferation activity. Subsequently, adjuvant doxorubicin plus ifosfamide chemotherapy was performed. No signs of recurrence were observed 12 months after the surgery.
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Harwood JL, Alexander JH, Mayerson JL, Scharschmidt TJ. Targeted Chemotherapy in Bone and Soft-Tissue Sarcoma. Orthop Clin North Am 2015; 46:587-608. [PMID: 26410647 DOI: 10.1016/j.ocl.2015.06.011] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Historically surgical intervention has been the mainstay of therapy for bone and soft-tissue sarcomas, augmented with adjuvant radiation for local control. Although cytotoxic chemotherapy revolutionized the treatment of many sarcomas, classic treatment regimens are fraught with side effects while outcomes have plateaued. However, since the approval of imatinib in 2002, research into targeted chemotherapy has increased exponentially. With targeted therapies comes the potential for decreased side effects and more potent, personalized treatment options. This article reviews the evolution of medical knowledge regarding sarcoma, the basic science of sarcomatogenesis, and the major targets and pathways now being studied.
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Affiliation(s)
- Jared L Harwood
- Department of Orthopaedics, The Ohio State University, 725 Prior Hall, 376 West 10 Avenue, Columbus, OH 43210, USA
| | - John H Alexander
- Department of Orthopaedics, The Ohio State University, 725 Prior Hall, 376 West 10 Avenue, Columbus, OH 43210, USA
| | - Joel L Mayerson
- Department of Orthopaedics, The Ohio State University, 725 Prior Hall, 376 West 10 Avenue, Columbus, OH 43210, USA.
| | - Thomas J Scharschmidt
- Department of Orthopaedics, The Ohio State University, 725 Prior Hall, 376 West 10 Avenue, Columbus, OH 43210, USA
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Berzal Cantalejo MF, Herranz-Torrubiano AM, Cuenca-González C. [Soft tissue tumours: The dreaded sarcoma]. Semergen 2015; 42:126-8. [PMID: 25869411 DOI: 10.1016/j.semerg.2015.01.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Revised: 01/15/2015] [Accepted: 01/16/2015] [Indexed: 11/20/2022]
Affiliation(s)
- M F Berzal Cantalejo
- Especialista en Medicina familiar y Comunitaria, Especialista en Anatomía Patológica, Servicio de Anatomía Patológica, Hospital General Río Carrión, Palencia, España.
| | - A M Herranz-Torrubiano
- Especialista en Medicina familiar y Comunitaria, Centro de Salud La Alameda de Osuna, Atención Primaria Área 4, Madrid, España
| | - C Cuenca-González
- Especialista en Medicina familiar y Comunitaria, Especialista en Medicina Física y Rehabilitación, Servicio de Medicina Física y Rehabilitación, Hospital Clínico San Carlos, Madrid, España
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HARATI KAMRAN, SLODNIK PAWEL, CHROMIK ANSGARMICHAEL, BEHR BJÖRN, GOERTZ OLE, HIRSCH TOBIAS, KAPALSCHINSKI NICOLAI, KLEIN-HITPASS LUDGER, KOLBENSCHLAG JONAS, UHL WALDEMAR, LEHNHARDT MARCUS, DAIGELER ADRIEN. Pro-apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells. Int J Oncol 2015; 46:1629-36. [DOI: 10.3892/ijo.2015.2854] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Accepted: 12/23/2014] [Indexed: 11/06/2022] Open
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Harrison DJ, Schwartz C. Survivorship. J Surg Oncol 2014; 111:648-55. [PMID: 25557722 DOI: 10.1002/jso.23844] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 10/13/2014] [Indexed: 01/04/2023]
Abstract
Significant therapeutic advances for soft tissue sarcomas allow increasing numbers of patients--adult and pediatric--to achieve long term survival. However, the harsh cytotoxic therapies are responsible for adverse physical and psychosocial effects that require long-term follow-up care, specific to survivorship issues. In the adult and pediatric patient population, guidelines for care developed by experts in comprehensive survivorship clinics are evolving to assist the practitioner while on-line supports bring information directly to the survivors.
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Styring E, Hartman L, Nilbert M, Rissler P, Rydholm A, von Steyern FV. Small soft tissue sarcomas do metastasize: identification of high-risk tumors. Ann Surg Oncol 2014; 21:4020-5. [PMID: 24903235 DOI: 10.1245/s10434-014-3806-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Indexed: 11/18/2022]
Abstract
BACKGROUND Small (≤ 5 cm) soft tissue sarcomas (STS) of the extremities and the trunk wall generally have a favorable prognosis. However, 1 of 10 patients do develop metastases, and we therefore aimed to determine predictors of metastasis in a population-based cohort of patients with small STSs. PATIENTS AND METHODS In the southern Sweden health care region, 848 adult patients with STS of the extremities or the trunk wall were diagnosed between 1986 and 2010. Of these, 243 STS (29 %) were ≤5 cm. Prognostic evaluation was performed in 229 patients with localized disease at diagnosis, 181 of whom had histologic high-grade tumors. RESULTS None of the 48 patients with low-grade tumors developed metastases, whereas 24 of 181 patients with high-grade tumors (13 %) tumors did. Presence of either tumor necrosis or vascular invasion predicted development of metastases with a hazard ratio of 2.9 (95 % CI, 1.0-7.9), and tumors with both factors had a hazard ratio of 12 (95 % CI, 4.1-37) for metastasis (adjusted for size). CONCLUSIONS Our population-based series of STSs ≤5 cm demonstrate an overall good prognosis with metastases developing in 13 % of the patients with high-grade tumors. Tumor necrosis and vascular invasion were the major predictors of metastatic disease in this subset. Tumors with both these risk factors metastasized in 8 of 18 patients, which corresponds to a 12-fold increased risk of metastasis. These findings suggest that although small STS generally are linked to a good prognosis, necrosis and vascular invasion are features indicating biologically aggressive tumors for which treatment and surveillance should equal that for larger tumors.
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Affiliation(s)
- Emelie Styring
- Department of Orthopedics, Department of Clinical Sciences, Lund University, Lund, Sweden,
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Bremjit PJ, Jones RL, Chai X, Kane G, Rodler ET, Loggers ET, Pollack SM, Pillarisetty VG, Mann GN. A Contemporary Large Single-Institution Evaluation of Resected Retroperitoneal Sarcoma. Ann Surg Oncol 2014; 21:2150-8. [DOI: 10.1245/s10434-014-3616-7] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Indexed: 01/30/2023]
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Behnke NK, Alamanda VK, Song Y, Archer KR, Halpern JL, Schwartz HS, Holt GE. Does postoperative infection after soft tissue sarcoma resection affect oncologic outcomes? J Surg Oncol 2013; 109:415-20. [PMID: 24284805 DOI: 10.1002/jso.23518] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 11/09/2013] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND OBJECTIVES Prior studies have demonstrated postoperative infection may confer a survival benefit after osteosarcoma resection. Our aim was to determine whether infection after soft tissue sarcoma resection has similar effects on metastasis, recurrence and survival. METHODS A retrospective review was conducted; 396 patients treated surgically for a soft tissue sarcoma between 2000 and 2008 were identified. Relevant oncologic data were collected. Fifty-six patients with a postoperative infection were compared with 340 patients without infection. Hazard ratios and overall cumulative risk were evaluated. RESULTS There was no difference in survival, local recurrence or metastasis between patients with or without a postoperative infection. Patients were evenly matched for age at diagnosis, gender, smoking status, and diabetes status. Tumor characteristics did not differ between groups in tumor size, location, depth, grade, margin status, stage, and histologic subtype. There was no difference in utilization of chemotherapy or radiation therapy between groups. From our competing risk model, only positive margin status significantly impacted the risk of local recurrence. An increase in tumor size corresponded to an increased risk of metastasis and death. CONCLUSIONS Postoperative infection neither conferred a protective effect, nor increased the risk of adverse oncologic outcomes after soft tissue sarcoma resection.
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Affiliation(s)
- Nicole K Behnke
- Division of Orthopaedic Surgery, University of Alabama at Birmingham Medical Center, Birmingham, Alabama
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Williams KJ, Hayes AJ. A guide to oncological management of soft tissue tumours of the abdominal wall. Hernia 2013; 18:91-7. [PMID: 24043554 DOI: 10.1007/s10029-013-1156-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Accepted: 09/06/2013] [Indexed: 02/02/2023]
Abstract
INTRODUCTION An abdominal mass is a common clinical presentation, and a small percentage of such patients will have an abdominal wall tumour with the two most common pathologies being fibromatosis and soft tissue sarcoma. METHODS Here we present the available literature on the diagnosis and management of both fibromatosis and soft tissue sarcoma, in the context of our experience in a tertiary referral centre for sarcoma. RESULTS AND DISCUSSION Appropriate cross-sectional imaging and a pre-operative tissue diagnosis by percutaneous core biopsy are necessary to define management. Desmoid fibromatosis can be managed initially by observation with serial imaging, with surgery being reserved for those patients who demonstrate progression. Soft tissue sarcoma can display a range of pathologies from relatively indolent tumours to locally aggressive sarcomas that can readily metastasise. An accurate pre-operative histological diagnosis and staging enables a multidisciplinary approach to management. This may include chemotherapy and radiotherapy, but the mainstay of treatment remains wide surgical resection and abdominal wall reconstruction. Patient outcomes are worse if referral is delayed or if the sarcoma is incompletely resected without an initial tissue diagnosis.
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Affiliation(s)
- K J Williams
- Academic Section of Vascular Surgery, Imperial College London, London, UK,
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Li GD, Kawashima H, Ogose A, Ariizumi T, Hotta T, Kuwano R, Urata Y, Fujiwara T, Endo N. Telomelysin shows potent antitumor activity through apoptotic and non-apoptotic cell death in soft tissue sarcoma cells. Cancer Sci 2013; 104:1178-88. [PMID: 23718223 DOI: 10.1111/cas.12208] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2013] [Revised: 05/08/2013] [Accepted: 05/08/2013] [Indexed: 01/09/2023] Open
Abstract
This study investigated the pathway underlying the antitumor activity of telomelysin, a telomerase-dependent, replication-selective oncolytic adenovirus, in soft tissue sarcoma cells. Treatment with telomelysin alone resulted in simultaneous induction of apoptosis and autophagy, whereas cotreatment with telomelysin and 3-methyladenine significantly reduced cell viability and increased apoptosis and the cellular ATP level compared to treatment with telomelysin alone, indicating that telomelysin-mediated autophagy is a death-protective but not death-promoting process. Cotreatment with Z-Val-Ala-Asp-CH2F significantly increased cellular ATP depletion compared to telomelysin-alone treatment while inhibiting telomelysin-induced apoptosis and having no significant effect on cell viability, indicating that it promotes transition from apoptotic to necrotic cell death.
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Affiliation(s)
- Gui-Dong Li
- Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Kandel R, Coakley N, Werier J, Engel J, Ghert M, Verma S. Surgical margins and handling of soft-tissue sarcoma in extremities: a clinical practice guideline. ACTA ACUST UNITED AC 2013; 20:e247-54. [PMID: 23737694 DOI: 10.3747/co.20.1308] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
QUESTIONS In limb salvage surgery for extremity soft-tissue sarcoma (sts), what is an adequate surgical margin?What is the appropriate number of samples to take from the margins of a surgical resection specimen?What is the appropriate handling of surgical resection specimens? BACKGROUND Surgery is the primary treatment for extremity sts. The combination of radiotherapy with surgery allows for limb salvage by using radiation to biologically "sterilize" microscopic extensions of tumour and to spare neurovascular and osseous structures. Adjuvant chemotherapy in sts-except for rhabdomyosarcoma and Ewing sarcoma-continues to be controversial. METHODS The medline and embase databases (1975 to June 2011) and the Cochrane Library were searched for pertinent studies. The Web sites of the main guideline organizations and the American Society of Clinical Oncology conference proceedings (2007-2010) were also searched. RESULTS AND CONCLUSIONS Thirty-three papers, including four guidelines, one protocol, and one abstract, were eligible for inclusion. The data suggest that patients with clear margins have a better prognosis, but no prospective studies have indicated how wide margins should be. In limb-salvage surgery for extremity sts, the procedure should be planned to achieve a clear margin. However, to preserve functionality, surgery may result in a very close (<1 cm) or even microscopically positive margin. In this circumstance, the use of preoperative or postoperative radiation should be considered. No studies described the optimal number of tissue sections required to assess adequacy of excision nor the appropriate handling of surgical resection specimens. The Sarcoma Disease Site Group made its recommendations based on expert opinion and consensus.
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Affiliation(s)
- R Kandel
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON
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Matushansky I, Dela Cruz F, Insel BJ, Hershman DL, Neugut AI. Chemotherapy Use in Elderly Patients with Soft Tissue Sarcoma: A Population-based Study. Cancer Invest 2013; 31:83-91. [DOI: 10.3109/07357907.2012.756112] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Karlisch C, Harati K, Chromik AM, Bulut D, Klein-Hitpass L, Goertz O, Hirsch T, Lehnhardt M, Uhl W, Daigeler A. Effects of TRAIL and taurolidine on apoptosis and proliferation in human rhabdomyosarcoma, leiomyosarcoma and epithelioid cell sarcoma. Int J Oncol 2013; 42:945-56. [PMID: 23338823 DOI: 10.3892/ijo.2013.1772] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Accepted: 12/07/2012] [Indexed: 11/05/2022] Open
Abstract
Soft tissue sarcomas (STS) are a heterogeneous group of malignant tumours representing 1% of all malignancies in adults. Therapy for STS should be individualised and multimodal, but complete surgical resection with clear margins remains the mainstay of therapy. Disseminated soft tissue sarcoma still represents a therapeutic dilemma. Commonly used chemotherapeutic agents such as doxorubicin and ifosfamide have proven to be effective in fewer than 30% in these cases. Therefore, we tested the apoptotic and anti-proliferative in vitro effects of TNF-related apoptosis-inducing ligand (TRAIL) and taurolidine (TRD) on rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cell lines. Viability, apoptosis and necrosis were quantified by FACS analysis (propidium iodide/Annexin V staining). Gene expression was analysed by DNA microarrays and the results validated for selected genes by rtPCR. Protein level changes were documented by western blot analysis. Cell proliferation was analysed by BrdU ELISA assay. The single substances TRAIL and TRD significantly induced apoptotic cell death and decreased proliferation in rhabdomyosarcoma and epithelioid cell sarcoma cells. The combined use of TRAIL and TRD resulted in a synergistic apoptotic effect in all three cell lines, especially in rhabdomyosarcoma cells leaving 18% viable cells after 48 h of incubation (p<0.05). Analysis of the differentially regulated genes revealed that TRD and TRAIL influence apoptotic pathways, including the TNF-receptor associated and the mitochondrial pathway. Microarray analysis revealed remarkable expression changes in a variety of genes, which are involved in different apoptotic pathways and cross talk to other pathways at multiple levels. This in vitro study demonstrates that TRAIL and TRD synergise in inducing apoptosis and inhibiting proliferation in different human STS cell lines. Effects on gene expression differ relevantly in the sarcoma entities. These results provide experimental support for in vivo trials assessing the effect of TRAIL and TRD in STS and sustain the approach of individualized therapy.
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Affiliation(s)
- C Karlisch
- Department of Gynecology and Obstetrics, Marienhospital Witten, Ruhr-University, D-58452 Witten, Germany
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Adekola K, Agulnik M. Advances in Adjuvant Therapy of Gastrointestinal Stromal Tumors. Curr Oncol Rep 2012; 14:327-32. [DOI: 10.1007/s11912-012-0241-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
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Leitao MM, Zivanovic O, Chi DS, Hensley ML, O'Cearbhaill R, Soslow RA, Barakat RR. Surgical cytoreduction in patients with metastatic uterine leiomyosarcoma at the time of initial diagnosis. Gynecol Oncol 2012; 125:409-13. [PMID: 22366592 DOI: 10.1016/j.ygyno.2012.02.014] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2012] [Revised: 02/10/2012] [Accepted: 02/13/2012] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To determine whether cytoreduction is associated with improved outcome in patients newly diagnosed with metastatic uterine leiomyosarcoma (LMS). METHODS We retrospectively identified all patients treated at our institution for high-grade uterine LMS with extrauterine disease at the time of initial diagnosis from 7/1/82 to 7/31/07. Pattern of disease spread was classified as intraperitoneal (IP) or extraperitoneal (EP). Progression-free survival (PFS) and overall survival (OS) were determined from date of initial surgery using Kaplan-Meier estimates. RESULTS We identified 96 cases. Median age was 54 years (range, 23-81). IP disease was seen in 48 (50%) and EP in 48 (50%). A complete gross resection of all tumor was achieved in 41/84 (49%). Recurrence or progression was noted in 93 (97%); 81 (84%) have died. Median PFS and OS for the entire cohort was 9.7 months (range, 6.7-10.9) and 20.2 months (range, 15.5-24.8), respectively. All 8 non-surgical cases died within 30 months of diagnosis. Median PFS was 14.2 months (range, 11.4-16.9) for those with a complete gross resection versus 6.8 months (range, 4.1-9.5) for those with any residual disease (P=0.002). Median OS was 31.9 months (range, 3.3-60.4) versus 20.2 months (range, 11.8-28.6), respectively (P=0.04). On multivariate analysis, no residual disease was independently associated with PFS when adjusting for disease distribution (IP vs EP) and the use of chemotherapy but not OS. CONCLUSIONS Surgical cytoreduction of metastatic uterine LMS was independently associated with PFS but not OS in cases selected for surgery. The improvement in PFS must be weighed against the morbidity of surgery.
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Affiliation(s)
- Mario M Leitao
- Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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Abstract
Sarcomas are a heterogeneous group of relatively rare mesenchymal neoplasms. They can be grouped into two general categories: soft tissue sarcoma (STS) and primary bone sarcoma, which are treated differently. Because sarcomas are relatively rare and complex with a wide variety of different histopathologic subtypes, evaluation by multidisciplinary teams who have expertise in the field is recommended. Treatment guidelines for the use of chemotherapy in patients with STS and bone sarcoma have been published by the National Comprehensive Cancer Network. The role of adjuvant chemotherapy in resected STS remains controversial. Although chemotherapy improves disease-free survival, the long-term overall survival benefit remains unproven. Chemotherapy is typically used as palliative treatment for most subtypes of metastatic STS. In contrast, chemotherapy has a proven role in the treatment of primary bone tumors and Ewing sarcoma, but it has not demonstrated efficacy in the treatment of chondrosarcoma. The standard chemotherapy regimens used in sarcoma are associated with significant toxicity, including long-term complications. Less intense and less toxic regimens are the focus of ongoing clinical research. Newer cytotoxic agents with an improved safety profile, such as trabectedin and palifosfamide, are currently in development. Future research needs to focus on identification of subpopulations of patients that are most likely to benefit from chemotherapy.
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Affiliation(s)
- David R D'Adamo
- Sarcoma and Bone Cancer Treatment Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
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Soini E. Cost-utility and expected value of perfect information related to trabectedin in the treatment of metastatic soft-tissue sarcoma: the publicly funded comments explored. Ann Oncol 2011; 22:1465-1466. [DOI: 10.1093/annonc/mdr268] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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