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Article ; Online: Management of Vascular Sarcoma.

Subramaniam, Aparna / Giani, Claudia / Napolitano, Andrea / Ravi, Vinod / Frezza, Anna Maria / Jones, Robin L

Surgical oncology clinics of North America

2022 Volume 31, Issue 3, Page(s) 485–510

Abstract: Vascular sarcomas encompass 3 well-defined sarcoma types: hemangioendothelioma, Kaposi sarcoma, and angiosarcoma. These distinct types are exceedingly rare and very different in terms of clinical behavior, biological features, and treatment approach. ... ...

Abstract	Vascular sarcomas encompass 3 well-defined sarcoma types: hemangioendothelioma, Kaposi sarcoma, and angiosarcoma. These distinct types are exceedingly rare and very different in terms of clinical behavior, biological features, and treatment approach. Because of this rarity and heterogeneity, it is crucial that vascular sarcomas are treated in sarcoma reference centers or networks, in order to ensure optimal management. The diversity of vascular sarcomas also needs to be taken into account in the design of clinical trials, in order to produce meaningful results that can be consistently translated into everyday clinical practice.
MeSH term(s)	Hemangioendothelioma ; Hemangioendothelioma, Epithelioid ; Hemangiosarcoma/therapy ; Humans ; Sarcoma/therapy ; Soft Tissue Neoplasms
Language	English
Publishing date	2022-05-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1196919-2
ISSN	1558-5042 ; 1055-3207
ISSN (online)	1558-5042
ISSN	1055-3207
DOI	10.1016/j.soc.2022.03.014
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Article ; Online: Tazemetostat for advanced epithelioid sarcoma: current status and future perspectives.

Simeone, Noemi / Frezza, Anna Maria / Zaffaroni, Nadia / Stacchiotti, Silvia

Future oncology (London, England)

2020 Volume 17, Issue 10, Page(s) 1253–1263

Abstract: Epithelioid sarcoma (ES) is an aggressive ultra-rare soft-tissue sarcoma marked by SMARCB1/INI1 deficiency. SMARCB1/INI1 deficiency leads to elevated expression of EZH2, a component of polycomb repressive complex 2, which mediates gene silencing by ... ...

Abstract	Epithelioid sarcoma (ES) is an aggressive ultra-rare soft-tissue sarcoma marked by SMARCB1/INI1 deficiency. SMARCB1/INI1 deficiency leads to elevated expression of EZH2, a component of polycomb repressive complex 2, which mediates gene silencing by catalyzing H3K27me3. Tazemetostat is an oral, SAM-competitive inhibitor of EZH2, whose blockade prevents the methylation of histone H3K27, thus decreasing the growth of EZH2 mutated or over-expressing cancer cells. Tazemetostat has been approved for the treatment of patients aged 16 years and older with metastatic or advanced ES not eligible for complete resection, based on the positive results of a single-arm Phase II basket study. Tazemetostat though represents a new treatment option for ES patients, although clinical/molecular predictors of response are still to be identified. The combination of tazemetostat with other drugs like doxorubicin and immunotherapeutic agents is currently under investigation in ES patients.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzamides/administration & dosage ; Benzamides/adverse effects ; Benzamides/therapeutic use ; Biphenyl Compounds/administration & dosage ; Biphenyl Compounds/adverse effects ; Biphenyl Compounds/therapeutic use ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Histones/metabolism ; Humans ; Morpholines/administration & dosage ; Morpholines/adverse effects ; Morpholines/therapeutic use ; Pyridones/administration & dosage ; Pyridones/adverse effects ; Pyridones/therapeutic use ; Sarcoma/drug therapy ; Sarcoma/etiology ; Sarcoma/mortality ; Sarcoma/pathology ; Soft Tissue Neoplasms/drug therapy ; Soft Tissue Neoplasms/mortality ; Soft Tissue Neoplasms/pathology ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Benzamides ; Biphenyl Compounds ; Histones ; Morpholines ; Pyridones ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; tazemetostat (Q40W93WPE1)
Language	English
Publishing date	2020-12-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2020-0781
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Article ; Online: Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

Danieli, Maria / Barretta, Francesco / Radaelli, Stefano / Fiore, Marco / Sangalli, Claudia / Barisella, Marta / Palassini, Elena / Miceli, Rosalba / Frezza, Anna Maria / Callegaro, Dario / Collini, Paola / Casali, Paolo Giovanni / Stacchiotti, Silvia / Gronchi, Alessandro

Cancer

2023 Volume 129, Issue 21, Page(s) 3417–3429

Abstract: Background: To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS).: Methods: All ... ...

Abstract	Background: To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). Methods: All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. Results: Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p = .09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. Conclusion: In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.
Language	English
Publishing date	2023-07-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34945
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Article ; Online: Phytochemical analysis of

Tomassini, Lamberto / Ventrone, Antonio / Frezza, Claudio / Fabbri, Anna Maria / Fortuna, Stefano / Volpe, Maria Teresa / Cometa, Maria Francesca

Natural product research

2020 Volume 35, Issue 24, Page(s) 5794–5800

Abstract: One flavonoid (quercetin, ...

Abstract	One flavonoid (quercetin,
MeSH term(s)	Acetylcholinesterase ; Butyrylcholinesterase ; Chalcones/pharmacology ; Cholinesterase Inhibitors/pharmacology ; Phytochemicals/pharmacology ; Viburnum/chemistry
Chemical Substances	Chalcones ; Cholinesterase Inhibitors ; Phytochemicals ; Acetylcholinesterase (EC 3.1.1.7) ; Butyrylcholinesterase (EC 3.1.1.8) ; dihydrochalcone (H5W525SX7Q)
Language	English
Publishing date	2020-10-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2185747-7
ISSN	1478-6427 ; 1478-6419
ISSN (online)	1478-6427
ISSN	1478-6419
DOI	10.1080/14786419.2020.1837814
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Article ; Online: Highlights in soft tissue sarcomas and gastrointestinal stromal tumours (GIST) trials reported at ASCO 2017 Annual Meeting.

Frezza, Anna Maria / Stacchiotti, Silvia / Gronchi, Alessandro

BMC medicine

2017 Volume 15, Issue 1, Page(s) 160

Abstract: Herein, we summarise the results of the most relevant studies presented at the 2017 ASCO Annual Meeting in the field of soft tissue sarcomas (STSs) and gastrointestinal stromal tumours (GISTs). Innovations on the management of localised disease, ... ...

Abstract	Herein, we summarise the results of the most relevant studies presented at the 2017 ASCO Annual Meeting in the field of soft tissue sarcomas (STSs) and gastrointestinal stromal tumours (GISTs). Innovations on the management of localised disease, highlights from the different experiences in the metastatic setting and large studies on rare histologies will be included. Special attention will be paid to results on immunotherapy, antiangiogenics use in histology with limited sensitivity to standard chemotherapy and new compounds. The preliminary results on the impact of the next generation sequencing in the everyday management of STS and GIST patients will be also discussed.
MeSH term(s)	Gastrointestinal Neoplasms/therapy ; Gastrointestinal Stromal Tumors/therapy ; Humans ; Sarcoma/pathology ; Sarcoma/therapy
Language	English
Publishing date	2017-08-22
Publishing country	England
Document type	Clinical Conference ; Journal Article
ISSN	1741-7015
ISSN (online)	1741-7015
DOI	10.1186/s12916-017-0931-4
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Article: Phytochemical analysis of Viburnum davidii Franch. and cholinesterase inhibitory activity of its dihydrochalcones

Tomassini, Lamberto / Ventrone, Antonio / Frezza, Claudio / Fabbri, Anna Maria / Fortuna, Stefano / Volpe, Maria Teresa / Cometa, Maria Francesca

Natural product research. 2021 Dec. 17, v. 35, no. 24

2021

Abstract: One flavonoid (quercetin, 1) and three dihydrochalcones (6''-O-p-hydroxybenzoyl-davidioside, 2, 4'-O-methyl-davidioside, 3, and davidioside, 4) were isolated from the leaves and young branches of Viburnum davidii Franch. All the structures were ... ...

Abstract	One flavonoid (quercetin, 1) and three dihydrochalcones (6''-O-p-hydroxybenzoyl-davidioside, 2, 4'-O-methyl-davidioside, 3, and davidioside, 4) were isolated from the leaves and young branches of Viburnum davidii Franch. All the structures were identified by comparison of their spectroscopic data (NMR and MS) with those present in literature. In addition, compounds 2–4 were evaluated for their cholinesterase inhibitory (ChEI) activity, for the first time. Accordingly, compounds 2 and 4 showed significant inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC₅₀ values equal to 36.883 and 39.274 µM, respectively for the former and 39.504 and 43.101 µM, respectively for the latter.
Keywords	Viburnum ; acetylcholinesterase ; cholinesterase ; quercetin ; research ; spectral analysis
Language	English
Dates of publication	2021-1217
Size	p. 5794-5800.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	2185747-7
ISSN	1478-6427 ; 1478-6419
ISSN (online)	1478-6427
ISSN	1478-6419
DOI	10.1080/14786419.2020.1837814
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Article ; Online: Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new.

Frezza, Anna Maria / Stacchiotti, Silvia / Gronchi, Alessandro

BMC medicine

2017 Volume 15, Issue 1, Page(s) 109

Abstract: For metastatic soft tissue sarcoma (STS) patients not eligible for surgery, systemic treatments, including standard chemotherapy and newer biological compounds, still play the most relevant role in the management of the disease. An anthracycline and ... ...

Abstract	For metastatic soft tissue sarcoma (STS) patients not eligible for surgery, systemic treatments, including standard chemotherapy and newer biological compounds, still play the most relevant role in the management of the disease. An anthracycline and alkylating agent combination has formed the cornerstone of chemotherapy in STS for more than 30 years, with its value over that of administration of anthracycline as a single agent still being debated. Efforts have been made to improve the activity and minimise the toxicity of the combination, as well as to explore the upfront efficacy of agents known to be active in sarcoma and to develop new biological compounds. Nevertheless, beyond the first line, evidence for medical treatment in STS is less robust and all the more driven by histology. Thus, the introduction of kinases and small molecule inhibitors in the treatment armamentarium for STS is a major achievement in this setting. Preliminary data on immunotherapy are also available and discussed in this review.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Humans ; Immunotherapy ; Sarcoma/therapy ; Soft Tissue Neoplasms/therapy
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2017-06-02
Publishing country	England
Document type	Journal Article ; Review
ISSN	1741-7015
ISSN (online)	1741-7015
DOI	10.1186/s12916-017-0872-y
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Article ; Online: Refining the Approach to Patients with Primary Soft Tissue Sarcoma of the Extremities and Trunk Wall: Outcome Improvement Over Time at a Single Institution.

Danieli, Maria / Barretta, Francesco / Fiore, Marco / Radaelli, Stefano / Sangalli, Claudia / Barisella, Marta / Stacchiotti, Silvia / Palassini, Elena / Miceli, Rosalba / Frezza, Anna Maria / Callegaro, Dario / Casali, Paolo Giovanni / Gronchi, Alessandro

Annals of surgical oncology

2022 Volume 29, Issue 5, Page(s) 3274–3286

Abstract: Background: The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients' cohort to assess ...

Abstract	Background: The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients' cohort to assess changes in outcomes over time for extremity and superficial trunk soft tissue sarcoma (ESTSTS) treated at a single referral center. Methods: All consecutive patients with primary localized adult-type ESTSTS surgically treated at the authors' institution between 1987 and 2017 were included and divided into group 1 (1987-2002) and group 2 (2003-2017) according to primary surgery year. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local recurrence (LR), and distant metastases (DM) were calculated in a competing-risks framework. DM-free survival (DMFS) and post-DM survival were also assessed. Results: The study identified 2382 patients. The median follow-up was 104 months (range, 63-127 months), and the post-DM follow-up was 76 months (range, 37-126 months). Since 2003, an increased adoption of preoperative treatments was observed: the use of chemotherapy, radiotherapy and combined chemoradiotherapy went from 10.5% to 23.7%, from 1.7% to 17.8%, and from 1% to 11.8% respectively. This change in treatment strategies was associated to an improvement in CCI-SSM (27.8% vs 19.5%; P < 0.001), CCI-LR (14.1 vs 7.5%; P < 0.001), DMFS (57.9% vs 65.8%; P = 0.004), and post-DM (12.2% vs 20.1%; P = 0.012), but not in CCI-DM. Conclusions: Increased adoption of preoperative treatments and greater availability of medical agents in the recent years were associated to better outcomes. New treatments are eagerly awaited for further improvement of outcome for ESTSTS patients because no major changes have been observed since 2003.
MeSH term(s)	Adult ; Extremities/pathology ; Follow-Up Studies ; Humans ; Neoplasm Recurrence, Local/pathology ; Retrospective Studies ; Sarcoma/pathology ; Soft Tissue Neoplasms/pathology ; Survival Rate
Language	English
Publishing date	2022-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-021-11189-2
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Zs.A 4042: Show issues

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Article ; Online: Networking in rare cancers: What was done, what's next.

Frezza, Anna Maria / Trama, Annalisa / Blay, Jean-Yves / Casali, Paolo G

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2018 Volume 45, Issue 1, Page(s) 16–18

Abstract: Rare cancers represent approximately one fourth of all cancers. Despite being a heterogeneous group of diseases, they share similar problems including lack of expertise, issues in quality of care, discrepancies in outcome and limitations in research. ... ...

Abstract	Rare cancers represent approximately one fourth of all cancers. Despite being a heterogeneous group of diseases, they share similar problems including lack of expertise, issues in quality of care, discrepancies in outcome and limitations in research. Traditionally, centralization of rare cancer patients to dedicated reference centres has been recommended to ensure expertise, multidisciplinarity and access to innovation. However, centralization entails health migration, rationing of resources and a potential failure in routine care. By ensuring appropriate care to all patients regardless the point of access, networking seems the most appropriate answer to the problem of rare cancers. The launch of the Joint Action on Rare Cancers as well as the recent establishment of the European Reference Networks represent for the first time a concrete opportunity to make networking a reality and ultimately reduce disparities and improve outcome in these diseases.
MeSH term(s)	Delivery of Health Care/organization & administration ; Europe ; Humans ; Intersectoral Collaboration ; Neoplasms/therapy ; Rare Diseases/therapy
Language	English
Publishing date	2018-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2018.03.030
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Zs.A 1149: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Effectiveness of irinotecan plus trabectedin on a desmoplastic small round cell tumor patient-derived xenograft.

Zuco, Valentina / Pasquali, Sandro / Tortoreto, Monica / Percio, Stefano / Doldi, Valentina / Barisella, Marta / Collini, Paola / Dagrada, Gian Paolo / Brich, Silvia / Gasparini, Patrizia / Fiore, Marco / Casanova, Michela / Frezza, Anna Maria / Gronchi, Alessandro / Stacchiotti, Silvia / Ferrari, Andrea / Zaffaroni, Nadia

Disease models & mechanisms

2023 Volume 16, Issue 6

Abstract: This study exploited a novel patient-derived xenograft (PDX) of desmoplastic small round cell tumor (DSRCT), which reproduces histomorphological and molecular characteristics of the clinical tumor, to assess the activity of cytotoxic and targeted ... ...

Abstract	This study exploited a novel patient-derived xenograft (PDX) of desmoplastic small round cell tumor (DSRCT), which reproduces histomorphological and molecular characteristics of the clinical tumor, to assess the activity of cytotoxic and targeted anticancer agents. Antitumor effect was moderate for doxorubicin, pazopanib and larotrectenib [maximum tumor volume inhibition (max TVI), 55-66%], while trabectedin had higher activity (max TVI, 82%). Vinorelbine, irinotecan and eribulin achieved nearly complete tumor growth inhibition (max TVI, 96-98%), although tumors regrew after the end of treatment. The combination of irinotecan with either eribulin or trabectedin resulted in complete responses, which were maintained until the end of the experiment for irinotecan plus trabectedin. Irinotecan-based combinations nearly abrogated the expression of proteins of the G2/M checkpoint, preventing cell entrance in mitosis, and induced apoptotic and necroptotic cell death. Consistently, irinotecan plus trabectedin resulted in reprogramming of DSCRT transcriptome, with downregulation of E2F targets, G2/M checkpoint and mitotic spindle gene sets. This study emphasizes the importance of patient-derived preclinical models to explore new treatments for DSRCT and fosters clinical investigation into the activity of irinotecan plus trabectedin.
MeSH term(s)	Humans ; Trabectedin/therapeutic use ; Trabectedin/pharmacology ; Irinotecan/pharmacology ; Irinotecan/therapeutic use ; Desmoplastic Small Round Cell Tumor/drug therapy ; Desmoplastic Small Round Cell Tumor/pathology ; Heterografts ; Antineoplastic Agents/therapeutic use
Chemical Substances	Trabectedin (ID0YZQ2TCP) ; Irinotecan (7673326042) ; eribulin (LR24G6354G) ; Antineoplastic Agents
Language	English
Publishing date	2023-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.049649
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