Stochastic atomic acceleration during the X-ray-induced fluidization of a silica glass.

The X-ray-induced, nonthermal fluidization of the prototypical SiO2 glass is investigated by X-ray photon correlation spectroscopy in the small-angle scattering range. This process is initiated by the absorption of X-rays and leads to overall atomic displacements which reach at least few nanometers at temperatures well below the glass transition. At absorbed doses of ∼5 GGy typical of many modern X-ray-based experiments, the atomic displacements display a hyperdiffusive behavior and are distributed according to a heavy-tailed, Lévy stable distribution. This is attributed to the stochastic generation of X-ray-induced point defects which give rise to a dynamically fluctuating potential landscape, thus providing a microscopic picture of the fluidization process.

New Molecular Insights, and the Role of Systemic Therapies and Collaboration for Treatment of Epithelioid Hemangioendothelioma (EHE).

OPINION STATEMENT: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated vascular sarcoma. EHE can have different clinical presentations from indolent to rapidly evolving cases, behaving as a high-grade sarcoma. Serosal effusion and systemic symptoms such as fever and severe pain are known as adverse prognostic factors; however, outcome prediction at disease onset remains a major challenge. In spite of its rarity, an international collaborative effort is in place with the support of patient advocates to increase the knowledge of EHE biology, develop new treatment options, and improve patient access to new active medications. Currently, systemic therapies are indicated only for patients suffering from progressive and/or symptomatic disease and in patients with a high risk of organ dysfunction. Standard systemic agents available so far for treatment of sarcomas, and in particular anthracycline-based chemotherapy, have marginal activity in EHE. On this background, EHE patients should be always considered for clinical study when available. The MEK inhibitor trametinib has been recently investigated prospectively in advanced EHE showing some activity, but the publication of the full dataset is still awaited to better interpret the results. Besides, there are data on response to antiangiogenics such as sorafenib and bevacizumab and, from retrospective studies, interferon, thalidomide, and sirolimus. Unfortunately, none of these agents is formally approved for EHE patients and access to treatments varies greatly between countries causing a huge disparity in patient care from one country to another.

Data-Driven Insights through Industrial Retrofitting: An Anonymized Dataset with Machine Learning Use Cases.

Small and medium-sized enterprises (SMEs) often encounter practical challenges and limitations when extracting valuable insights from the data of retrofitted or brownfield equipment. The existing literature fails to reflect the full reality and potential of data-driven analysis in current SME environments. In this paper, we provide an anonymized dataset obtained from two medium-sized companies leveraging a non-invasive and scalable data-collection procedure. The dataset comprises mainly power consumption machine data collected over a period of 7 months and 1 year from two medium-sized companies. Using this dataset, we demonstrate how machine learning (ML) techniques can enable SMEs to extract useful information even in the short term, even from a small variety of data types. We develop several ML models to address various tasks, such as power consumption forecasting, item classification, next machine state prediction, and item production count forecasting. By providing this anonymized dataset and showcasing its application through various ML use cases, our paper aims to provide practical insights for SMEs seeking to leverage ML techniques with their limited data resources. The findings contribute to a better understanding of how ML can be effectively utilized in extracting actionable insights from limited datasets, offering valuable implications for SMEs in practical settings.

Weekly cisplatin with or without imatinib in advanced chordoma: A retrospective case-series analysis from the Italian Rare Cancers Network.

BACKGROUND: To report on a retrospective case-series analysis of weekly cisplatin (wCDDP) as a single agent or combined with imatinib (wCDDP/I) in patients with advanced chordoma treated within the Italian Rare Cancer Network. METHODS: Adult patients with a diagnosis of advanced, brachyury-positive chordoma, treated from April 2007 to October 2020 with wCDDP or wCDDP/I were retrospectively identified. Imatinib was withheld at the same time as wCDDP. Response according to Response Evaluation Criteria in Solid Tumors, overall survival (OS), and progression-free survival (PFS) were analyzed. RESULTS: Thirty-three consecutive patients were identified (wCDDP as front-line n = 8 [24.2%]; wCDDP as a further line n = 25 [75.8%]; prior imatinib n = 25 [75.8%]; evidence of progression before starting wCDDP n = 33). Of 32 patients evaluable for response (wCDDP, n = 22 [68.8%]; wCDDP/I, n = 10 [31.3%]), best response was stable disease (SD) in 27 patients (84.3%) and progression in 5 patients (15.6%). At a median follow-up of 54 months, the median OS (m-OS) was 30.3 months (interquartile range [IQR], 18.1-56.6), the m-PFS was 8.0 months (IQR, 5.1-17.0), the 6-month PFS rate was 65.2%, and the 12-month PFS rate was 30.3%. Of 22 patients who received wCDDP, the best response was SD in 18 patients (81.8%) and progression in 4 patients (18.2%), and the m-PFS was 8.0 months (IQR, 5.1-17.0 months). Of 10 patients who received treatment with wCDDP/I, the best response was SD in 9 patients (90%) and progression in 1 patient (10%), and the m-PFS was 9.3 months (IQR, 4.9-26.5 months). CONCLUSIONS: This series suggests that wCDDP, both as a single agent and combined with imatinib, has antitumor activity in chordoma. Although no dimensional responses were observed, 65% and 30% of previously progressive patients were progression-free at 6 and 12 months, respectively. A prospective study is warranted.

Activity of sirolimus in patients with progressive epithelioid hemangioendothelioma: A case-series analysis within the Italian Rare Cancer Network.

BACKGROUND: The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. METHODS: From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. RESULTS: All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. CONCLUSIONS: The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.

Primary pleural epithelioid hemangioendothelioma: case report and review of the literature.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with an unpredictable clinical behavior. Pleural EHEs have been associated with poor response to treatment and reduced survival. To date, no standard treatment for EHE is available. Here we report the case of a 53-year-old man who underwent radical surgery for a symptomatic primary pleural EHE. Clinical presentation was characterized by chronic pain in the left hemithorax with transitory flare, anemia, weight loss and progressive worsening of clinical conditions. After surgery, he resumed active life and normal daily activities and, at 8 months, 18F-FDG PET and computed tomography scan showed no radiological evidence of recurrent disease. Clinical signs of this rare disease, histological features, imaging findings and functional imaging are discussed. We also report a summary of other cases with resected pleural EHE and we briefly review the role of chemotherapeutic, immunomodulatory and antiangiogenic drugs for advanced disease.

Pharmacokinetics, safety, and activity of trabectedin as first-line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group.

BACKGROUND: Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline-based chemotherapy. Trabectedin is registered as a second-line treatment for advanced STS and is characterized by a favorable safety profile. METHODS: The aim of this single-arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3-1.5 mg/m2 ) as a first-line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline-based chemotherapy. The coprimary endpoints were progression-free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics. RESULTS: Twenty-four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74-83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3-6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%-81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%-57%]) experienced CLTs. Trabectedin Cmax , half-life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2 ), and 1460 L/m2 (SD, 561 L/m2 ), respectively. CONCLUSION: Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data.

Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network.

BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.

The Activity of Chemotherapy in Inflammatory Myofibroblastic Tumors: A Multicenter, European Retrospective Case Series Analysis.

BACKGROUND: This study aimed to review the activity of cytotoxic chemotherapy in patients with inflammatory myofibroblastic tumors (IMTs) treated at nine European sarcoma reference centers. MATERIALS AND METHODS: Patients of any age, with histologically proven IMT, treated with anthracycline-based methotrexate plus/minus vinorelbine/vinblastine (MTX-V) or other chemotherapeutic regimens between 1996 and 2018 were retrospectively reviewed. Diagnosis was confirmed at the local level by an expert pathologist. Response was retrospectively assessed by local investigators by RECIST v1.1. Progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) were computed by Kaplan-Meier method. RESULTS: Thirty-eight patients were included. Twenty-five patients (8 localized, 17 advanced disease) received an anthracycline-based regimen; 21 were evaluable for response. Overall response rate (ORR) was 10/21 (47.6%). At a 70.8-month median follow-up (FU), median RFS and median OS were not reached (NR) in patients with localized disease; median PFS and median OS were 6.3 (interquartile range [IQR]: 1.9-13.4) and 21.2 (IQR: 7.7-40.7) months in patients with advanced disease. Thirteen patients received MTX-V (4 localized, 9 advanced disease), all evaluable for response. ORR was 7/13 (53.8%). At a 56.6-month median FU, median RFS and median OS were 42.5 (IQR: 12.9-61.2) months and NR (no death events) in patients with localized disease, and NR (IQR: 24.9 to NR) and 83.4 months (IQR: 83.4 to NR) in patients with advanced disease. In the "other-regimens group," responses were seen in 3/4 patients treated with oral cyclophosphamide and 1/2 with docetaxel/gemcitabine. CONCLUSION: Anthracycline-based and MTX-V regimens are very effective in IMT, with a similar ORR in both groups. MTX-V achieved a prolonged disease control. Responses were also seen with oral cyclophosphamide and docetaxel/gemcitabine, but few patients were treated with these schedules. IMPLICATIONS FOR PRACTICE: Inflammatory myofibroblastic tumor (IMT) is an ultrarare sarcoma with known sensitivity to anaplastic lymphoma kinase (ALK) inhibitors in ALK-fused cases, although ALK inhibitors are not licensed in the disease. The current knowledge on the activity of cytotoxic chemotherapy is limited. This multi-institutional retrospective study on pediatric and adult patients with IMT shows that cytotoxic chemotherapy, and in particular anthracycline-based and methotrexate plus/minus vinorelbine/vinblastine regimens, represents a treatment option and can be considered in IMT patients irrespectively from ALK status. This study provides a benchmark for future studies on new medical therapies.

Standard treatment and emerging drugs for managing synovial sarcoma: adult's and pediatric oncologist perspective.

INTRODUCTION: in this review we discuss the standard of care for both pediatric and adult synovial sarcoma (SS), the prognostic differences between them, and the treatments available for localized and advanced diseases. We also overview the biology and the recent drugs under consideration in clinical trials on SS. Areas covered: we focus on new targeted therapies being investigated for advanced SS, especially anti-angiogenic drugs, and immunotherapy. We review all the published data and ongoing trials dedicated to SS or to soft tissue sarcoma in general, paying particular attention to the results obtained in SS patients. Expert opinion: we expect new treatment strategies to become available for SS in the near future. The ongoing and published trials on targeted therapies and immunotherapy mainly concern adult patients, but the somatic biology of pediatric SS has some similarities as in adult disease. A stronger cooperation between adult and pediatric oncologists in recent years has led to a more shared effort to find new treatment strategies for advanced SS patients, regardless of their age.

Preoperative Denosumab With Curettage and Cryotherapy in Giant Cell Tumor of Bone: Is There an Increased Risk of Local Recurrence?

BACKGROUND: Denosumab is a monoclonal RANKL antibody, which was originally introduced for the treatment of osteoporosis and bone metastases from solid tumors, but more recently has been used for treatment of giant cell tumor of bone (GCTB). In GCTB, denosumab has been used as a single agent in patients with inoperable tumors; it also has been used before surgery in some patients with the aim to downstage the tumor to facilitate a joint-preserving procedure (curettage) rather than a resection. However, few studies are available evaluating the benefits and risks of denosumab for the latter indication. QUESTIONS/PURPOSES: (1) Does preoperative treatment with denosumab reduce the risk of local recurrence in patients treated for GCTB? (2) Are there adverse effects of short-term denosumab use before surgery and, if so, what are they? METHODS: All patients with a diagnosis of GCTB surgically treated at our institution from June 2009 to June 2016 with curettage and cryotherapy were retrospectively evaluated to compare patients treated with curettage alone versus patients treated with curettage after preoperative therapy with denosumab. During that period, we treated 97 patients for GCTB; 30 patients were excluded because they received a resection; 34 patients were excluded because they received curettage without cryotherapy. Of the remaining 33 patients, four were excluded because they received denosumab only after surgery, one because she received zoledronic acid, one because she received a curettage after her refusal of a resection that was the advised procedure, two because they were lost to followup early, and four because they were treated for recurrence rather than a new diagnosis of GCTB. The remaining 21 patients were included. Twelve lesions had been treated with surgery after denosumab and nine with surgery alone. During the study period, we preferentially used denosumab for the more aggressive-looking lesions. After curettage, cryotherapy of the residual bone walls was performed with argon cryoprobes to -150° C after pouring gel into the cavity, and we then used cement (17 patients) or morcellized allograft (four patients). Tumors were Campanacci Grade 3 in eight of 12 patients in the denosumab group and in two of nine patients in the surgery-only group (p = 0.08), but the extent of epiphyseal juxtaarticular bone involvement was not different between the groups with the numbers available. Median followup was 39 months (range, 14-55 months) in the denosumab group and 27 months (range, 18-92 months) in the surgery-only group. We used chart review to record the proportion of patients in each treatment group who had a local recurrence and to tally adverse events. RESULTS: With the numbers available, there was no difference in the proportion of patients experiencing a recurrence (five of 12 in the denosumab group and one of nine in the surgery-only group; p = 0.18). We found no adverse effects associated with denosumab either during or after treatment; specifically, we found no alterations in electrolyte levels, blood count, or liver and renal function parameters. In this small series, no patient has developed osteonecrosis of the jaw. CONCLUSIONS: In this small series, use of denosumab before surgery for GCTB appeared to allow the reforming of a bone peripheral rim around the tumor, perhaps facilitating curettage rather than osteoarticular resection in some patients. However, we did not observe a decrease in the risk of local recurrence with the use of denosumab, suggesting that it may not decrease the aggressiveness of the disease; according to our preliminary results, we cannot exclude that the rate of local recurrence could be even higher after curettage in denosumab-treated patients than in nontreated patients, and until or unless larger studies demonstrate such a reduction, primary intralesional surgery without denosumab seems more prudent when curettage is feasible at presentation. We did not observe any adverse effects with denosumab, but we caution readers that this study was underpowered to detect even relatively common complications and relatively large differences in the risk of local recurrence. Future studies should evaluate denosumab prospectively; given the relative rarity of this tumor, we suspect multicenter studies are needed to achieve this. LEVEL OF EVIDENCE: Level III, therapeutic study.

Liposarcoma: Clinico-pathological analysis, prognostic factors and survival in a series of 307 patients treated at a single institution.

BACKGROUND AND OBJECTIVES: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma. METHODS: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed. RESULTS: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS). CONCLUSION: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS.

Damping of vibrational excitations in glasses at terahertz frequency: The case of 3-methylpentane.

We report a compared analysis of inelastic X ray scattering (IXS) and of low frequency Raman data of glassy 3-methylpentane. The IXS spectra have been analysed allowing for the existence of two distinct excitations at each scattering wavevector obtaining a consistent interpretation of the spectra. In particular, this procedure allows us to interpret the linewidth of the modes in terms of a simple model which relates them to the width of the first sharp diffraction peak in the static structure factor. In this model, the width of the modes arises from the blurring of the dispersion curves which increases approaching the boundary of the first pseudo-Brillouin zone. The position of the boson peak contribution to the density of vibrational states derived from the Raman scattering measurements is in agreement with the interpretation of the two excitations in terms of a longitudinal mode and a transverse mode, the latter being a result of the mixed character of the transverse modes away from the center of the pseudo-Brillouin zone.

Complete response after rechallenge with trabectedin in a patient with previously responding high-grade undifferentiated sarcoma.

Evidence supporting rechallenge in patients responding to first exposure to trabectedin is limited. We report on a 39-year-old woman with advanced high-grade undifferentiated sarcoma (US) retreated twice with trabectedin after first response. The patient presented in June 2006 with an abdominal mass originating from the rear fascia of the rectus abdominis. Staging examinations did not indicate metastases and she underwent surgery; pathology showed a high-grade (FNCLCC G3) US. Subsequently, the patient received five cycles of adjuvant chemotherapy with epirubicin and ifosfamide. In February 2009 a computed tomography (CT) scan showed an abdominal mass involving the transverse mesocolon. R0 surgery was performed. In September 2009, peritoneal lesions appeared. Trabectedin was initiated at a dose of 1.5 mg/m by a 24 h intravenous infusion every 3 weeks, without relevant toxicity. After six cycles (March 2010), CT and PET-CT scans showed complete disappearance of metastases. In February 2012, new secondary lesions in the subdiaphragmatic region and a peritoneal lesion appeared. We rechallenged the patient with the same schedule of trabectedin; a complete response was achieved after two cycles. In October 2013, new secondary lesions in the subdiaphragmatic region and a retroperitoneal lesion were found. We rechallenged with the same schedule of trabectedin; PET-CT scans after two cycles showed complete response on the subdiaphragmatic lesion. Radiotherapy on the retroperitoneal lesion was performed. The patient underwent a total of 18 cycles and remains free from radiologically detectable disease. We report complete radiological remission after two rechallenges with trabectedin in a patient with previously responding high-grade US.

Trabectedin in advanced synovial sarcomas: a multicenter retrospective study from four European institutions and the Italian Rare Cancer Network.

Treatment options for patients with metastatic synovial sarcoma are limited. Over recent years, trabectedin has emerged as an effective agent for patients with advanced soft tissue sarcomas resistant to anthracyclines and ifosfamide. The aim of this retrospective analysis was to study the efficacy of trabectedin in the subgroup of synovial sarcomas. A retrospective analysis was carried out on patients with advanced synovial sarcoma treated with trabectedin at four European reference sarcoma centers and within the Italian Rare Cancer Network between 2000 and 2013. Radiological response, progression-free, and overall survival, as well as serious and unexpected adverse events were retrospectively assessed. Sixty-one patients with metastatic synovial sarcoma were identified. The median number of previous chemotherapy regimens was 2 (range 1-6). Nine patients had a partial response, in addition to two minor responses, and 19 patients had stable disease, for an overall response rate of 15% and a tumor control rate of 50%. The median progression-free survival was 3 months, with 23% of patients free from progression at 6 months. The median progression-free survival in responding patients was 7 months. Trabectedin is a therapeutic option for palliative treatment of a subset of patients with metastatic synovial sarcoma.

The patient perspective on sirolimus for epithelioid hemangioendothelioma (EHE): results of a community survey highlighting the importance of equitable access to treatments.

Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, vascular sarcoma with clinical presentation ranging from an indolent to an aggressive form. Over 50% of patients present with metastatic disease, requiring systemic therapy, although no systemic therapies are specifically approved for EHE. Retrospective evidence supports the activity of mTOR inhibitors (e.g. sirolimus), although available only off-label. EHE patients and advocates are therefore working to support approval of effective treatments by collecting data on patient perspectives and experiences. Materials and methods: In February 2023, the EHE Rare Cancer Charity (UK) and The EHE Foundation (US), with other advocates, conducted a survey of perspectives and experiences of EHE patients regarding the use and accessibility of sirolimus. The survey consisted of 20 questions designed for individuals undergoing treatment, those who had been treated, or had never been treated with the drug. Widely promoted within the patient community, the online survey categorized patients into three cohorts for the analysis: liver transplant patients, non-transplant patients who had ever taken sirolimus and sirolimus-naïve non-transplant patients. Results: The survey evaluated data from 129 patient responses from 21 countries, mostly from USA, UK, Australia, and Canada (70%). The liver transplant, sirolimus and non-sirolimus cohorts were 16%, 25% and 59%, respectively. In the sirolimus group 66% reported treatment durations exceeding one year, with 16% exceeding five years, indicating the drug's efficacy. In the non-sirolimus group, the drug was not available for 42% and for 11% sirolimus was available but not selected for treatment because of its off-label status. Overall, 87% of all patients across all cohorts expressed the importance of the drug's availability as hugely or very important. Conclusion: The survey responses highlight the activity of sirolimus for EHE and the importance of securing a label extension for the drug delivering equitable access to this treatment for patients.

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

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.

The observational EURACAN prospective clinical registry dedicated to epithelioid hemangioendothelioma: The protocol of an international and collaborative effort on an ultra-rare entity.

INTRODUCTION: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. STUDY DESIGN: Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE. OBJECTIVES: To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. METHODS: Settings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. RESULTS: The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

EJSO educational Special issue from the TARPSWG - Standard medical treatment and new options in retroperitoneal sarcoma.

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.