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Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None of the authors has any interests to report directly related to this manuscript. Outside the scope of this manuscript: Elena Palassini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Giacomo Giulio Baldi, consulting fees from Eli Lilly, Pharmamar, AboutEvents; honoraria from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai, Istituto Gentili; support for attending meetings and/or travels from Novartis, Pharmamar, Eli Lilly; participation on advisory board from Pharmamar, Eli Lilly, Glaxo Smith Kline, Merck Sharp & Dome, Eisai. Sara Sulfaro, Marta Barisella, Giuseppe Bianchi, Domenico Campanacci, Marco Fiore, Marco Gambarotti, Massimiliano Gennaro, Carlo Morosi, no conflict of interests to declare. Federico Navarria, travel grants from Pharmamar, Boehringer Ingelheim. Claudia Sangalli, advisory board from Boehringer Ingelheim, Astra Zeneca. Rossella Bertulli, travel grants from PharmaMar. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alexia Bertuzzi, Roberto Biagini, Angela Bonadonna, Antonella Brunello, Dario Callegaro, no conflict of interests to declare. Ferdinando Cananzi, speaking fee from Istituto Gentili. Marco Cianchetti, Paola Collini(,) Danila Comandini, Annalisa Curcio, no conflict of interests to declare. Lorenzo D’Ambrosio, advisory board: PSI CRO Italy, GSK, AstraZeneca, Boehringer Ingelheim, Eisai. Meeting participation: GSK, AstraZeneca, PharmaMar. Martino De Pas, participation on advisory board from Glaxo Smith Kline, Boehringer Ingelheim. Trial support from: Pfizer, BluPrint Medicine, Gilead, Amgen, Merck. Angelo Paolo Dei Tos, no conflict of interests to declare. Virginia Ferraresi, Travel grants from PharmaMar, Gentili, Boehringer Ingelheim. Advisory Board: SERB Pharmaceuticals. Andrea Ferrari, Alessandro Franchi, no conflict of interests to declare. Anna Maria Frezza, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elena Fumagalli, Advisory Board from Deciphera Pharmaceuticals. Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Matteo Ghilli, Daniela Greto, no conflict of interests to declare. Giovanni Grignani, advisory board from Pharmamar, Incyte, Merck, Novartis, Deciphera,Bayer. Michele Guida, advisory board from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre. Toni ibrahim, advisory board and consultation fees from Amgen, Glaxosmithkline, PharMamar and Istituto Gentili. Travel grants from Istitaka Gentili and Pharmamar. Marco Krengli, Roberto Luksch, Andrea Marrari, Marinella Mastore, Alessandra Merlini, no conflict of interests to declare. Giuseppe Maria Milano, Advisory board from Bayer, GSK, SERBS Pharmaceuticals. Piera Navarria, Maria Abbondanza Pantaleo, Antonina Parafioriti, no conflict of interests to declare. Ilaria Pellegrini, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Elisabetta Pennacchioli, Marco Rastrelli, Elisabetta Setola, Salvatore Tafuto, Salvatore Turano, Sergio Valeri, Bruno Vincenzi, Viviana Vitolo, Andrei Ivanescu, Fiammetta Paloschi, no conflict of interests to declare. Paolo Giovanni Casali, Institutional Research Funding: Deciphera Pharmaceuticals, Blueprint Medicines, Cogent Biosciences, Amgen/Dompè, Bayer, GlaxoSmith Kline, Novartis, Pfizer, PharmaMar, Eisai, Eli Lilly, Advenchen Laboratories , Arog, Epizyme, Karyopharm Therapeutics, SpringWorks Ther,Daiichi Sankyo, Boehringer Ingelheim, Rain Therapeutics, Foghorn Ther Inc, Hutchinson MediPharam Lt, INBRX, PTC Ther. Alessandro Gronchi, no conflict of interests to declare. Silvia Stacchiotti, personal financial interests (honoraria, consultancy or advisory role): Aadi, Astex Pharmaceuticals, Bavarian Nordic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Gentili, GSK, Agenus, Ikena, MaxiVAX, Novartis, PharmaMar, Pharma Essentia, Rain Therapeutics, Servier. Support for attending meetings and/or travel Pharmamar; Institutional financial interests: Advenchen, Bayer, Blueprint, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, GSK, Hutchinson, Inhibrx, Karyopharm, Novartis, PharmaMar, Rain Therapeutics, SpringWorks; unpaid Member of the Scientifc Advisory Board of the Chordoma Foundation, Member of the Scientifc Advisory Board of the Desmoid Foundation, Member of the Scientifc Advisory Board of the Epithelioid Hemangioendothelioma Group, Member of the Scientifc Advisory Board of the Leiomyosarcoma Foundation., (Copyright © 2024. Published by Elsevier Ltd.)

Retroperitoneal soft tissue sarcomas mainly consist histologically of liposarcomas and leiomyosarcomas. For the liposarcoma subgroup, the local relapse rate seems to determine patients' overall prognosis. In contrast, leiomyosarcoma patients are challenged by the development of metastatic disease; therefore, effective systemic therapies are the cornerstone to improve patients' outcome. No doubt, the limited number of active regimens currently available makes the treatment of patients with locally advanced and/or metastatic disease challenging and results in the overall poor prognosis of this population. In this European Journal of Surgical Oncology Educational Special Issue from the Transatlantic Australasian RetroPeritoneal Sarcoma Working Group (TARPSWG), we aim to summarize state-of-the-art systemic treatments for patients with retroperitoneal sarcomas with a focus on the locally advanced and metastatic disease setting including conventional standard chemotherapies as well as new innovative treatment approaches in order to identify current unmet medical needs guiding the sarcoma community to initiate appropriate translational research projects and design innovative clinical trials., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: This case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants ("classic-type" and "proximal-type"). The value of a subtype-adapted grading system based on pathological features is explored., Methods: Data from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995-2015) were included. Centralised pathological review was performed. Classic-type ES was broken down into "high-grade" and "low-grade", according to number of mitoses, evidence of necrosis and nuclear atypia. Five- and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were estimated., Results: Fifty-two patients were included. 5- and 10-year OS estimates were 70% and 47% in the whole series, 57% and 37% in patients with proximal-type ES, 77% and 54% in patients with classic-type ES (P = 0.02). In classic-type ES, 5- and 10-year OS was higher for low-grade (95% and 72%, respectively) than high-grade tumours (P = 0.002). 5- and 10-year CCI estimates for LR were 21% and 33% in the whole series. 5- and 10-year CCI estimates for DM were 35% and 39% in the whole series, both 28% in classic-type ES, 47% and 59% in proximal-type ES (P = 0.03)., Conclusions: Suffering from a proximal- or a classic-type is the stronger predictor of outcome in patients with localised ES, with proximal-type ES patients having lower survival due to a higher tendency toward metastatic spreading. However, the "high-grade" classic-type ES was associated with outcomes close to proximal-type ES., Competing Interests: Declaration of competing interest AMF received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar and travel grants from PharmaMar. GGB received travel grants and advisory honoraria from Pharmamar and Eli Lilly, advisory honoraria from Eisai. NS received institutional clinical trials support from Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar. PGC has reported advisory roles for Deciphera Pharmaceuticals, Eisai, Eli Lilly, Nektar Therapeutics, speaker's honoraria from Eisai, Eli Lilly, Pfizer, PharmaMar, and conducted studies sponsored by Amgen Dompé, AROG Bayer, Blueprint Medicines, Eli Lilly, Daiichi Sankyo Pharma, Epizyme, GlaxoSmithKline, Novartis, Pfizer, PharmaMar. SSt has received honoraria from Eli Lilly, PharmaMar, Takeda; institutional research grants from Amgen Dompé, Advenchen, Bayer, Eli Lilly, Daiichi Sankyo Pharma, Epizyme Inc., Novartis, Pfizer and PharmaMar; travel grants from PharmaMar and has reported advisory/consultant roles for Bayer, Daiichi, Eli Lilly, Epizyme, Karyopharm, ImmuneDesign, Maxivax and PharmaMar. MS, SLV, FF, DC, DC, SP, AG, APDT, MG, MB, AP, LM have nothing to declare., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Sarcomas are rare malignant neoplasms that develop from mesenchymal cells and include a heterogeneous and large group of histological subtypes that may occur at any anatomical site. Soft tissue sarcomas (STS), the focus of this review, account for ≈70‒80% of sarcomas and represent <1% of all cancers. The heterogeneity of STS applies to both their topography and morphology, and 5-year survival can vary widely depending on disease stage and the complex interplay between anatomical site and histology for different STS subtypes. The rarity and heterogeneity of STS, together with other factors, such as the lack of clinical expertise often lead to difficulties and delays in making an accurate diagnosis and to the inappropriate management of each STS subtype. Therefore, this group of cancers requires special attention and approaches to diagnosis and treatment. Epidemiological data on STS are limited, and concerns have been raised regarding accurate registration of STS in cancer registries, including issues related to details of the histotypes. This review provides an overview of the epidemiology of STS in Italy, focusing on data from the Italian Association of Cancer Registries (AIRTUM), and compares findings with those from other European countries. Based on these data, and considering that STS is among the most common group of rare cancers, the relevance of multidisciplinary care for STS patients through reference centres, clinical networks and collaborative disease-specific groups is discussed., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers., Methods: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery., Results: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw., Conclusion: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose: FOLFOXIRI demonstrated higher efficacy compared to 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) as first-line treatment of metastatic colorectal cancer. We evaluated the outcome of second-line treatments among 196 patients treated with first-line FOLFOXIRI in three consecutive trials conducted by the Gruppo Oncologico Nord Ovest group., Patients and Methods: One hundred seventy-two of 196 patients so far progressed and 136 (79%) received second-line therapies: 32 (24%) were rechallenged with FOLFOXIRI, 52 (38%) were treated with irinotecan- or oxaliplatin-based doublets, and 52 (38%) received fluoropyrimidine plus mytomicin C or single-agent chemotherapy. Only 10 patients received bevacizumab (3) or cetuximab (7) with chemotherapy. Activity and efficacy data were collected and subgroup analyses were performed according to the regimen administered., Results: Overall response rate (RR) was 23%; median progression-free survival (PFS) and overall survival (OS) were 5.9 and 13.2 months, respectively. At an exploratory subgroup analysis, retreatment with FOLFOXIRI was associated with longer PFS (8.2 versus 6.3 months; P = .003, hazard ratio [HR] = 0.61) and OS (19.3 versus 14.0 months; P = .02, HR = 0.57) compared with doublets; single-agent chemotherapy or fluoropyrimidine plus mytomicin C was significantly lower in terms of RR (8%), PFS (3.0 months), and OS (8.7 months) compared with FOLFOXIRI or doublets., Conclusions: First-line FOLFOXIRI does not impair the efficacy of second-line treatments. In some patients rechallenge with FOLFOXIRI may represent a valid option, although potential imbalances in prognostic factors due to better patient selection should be considered., (Copyright © 2012 Elsevier Inc. All rights reserved.)