OBJECTIVE: Angiosarcoma (AS) is a rare malignancy with considerable heterogeneity seen in its aetiology, anatomical location, and clinicopathological behaviour. Diagnosis is often delayed and prognosis poor. The purpose of this study was to perform a retrospective review of all cases of AS over 10 years at a high-volume regional UK referral centre.
METHODS: We reviewed all cases of AS discussed at the sarcoma multidisciplinary meetings of University Hospitals Birmingham NHS Foundation Trust from September 2013 to August 2023. Demographic and clinicopathologic features at diagnosis, approaches to treatment, and outcomes were compared between four AS subtypes.
RESULTS: A total of 130 cases were identified. The median age at diagnosis was 71 years, with the majority being female (78%). The most common AS subtype was radiation-induced AS (RIAS) (n = 72; 55%), followed by primary cutaneous (n = 28; 22%), primary non-cutaneous (n = 25; 19%), and AS secondary to lymphoedema (n = 5; 4%). Metastases were present at diagnosis in 18% of patients. Treatment was with surgery in the majority of patients (71%). The median survival for the cohort was 30 months (95% CI 20-40), although this differed significantly by AS subtype (p < 0.001), ranging from 5 months in primary non-cutaneous AS to 76 months in RIAS.
CONCLUSIONS: RIAS is the most common AS subtype, with surgery the only potentially curative treatment modality. Overall prognosis varies significantly by subtype. An international consensus on classification of AS subtypes is required to allow meaningful comparisons across studies and/or a prospective multi-centre registry.

BACKGROUND: Angiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment.
METHODS: Propranolol was dosed 80 mg to 240 mg/day for 3 to 6 weeks according to a dose titration schedule. The primary endpoint was clinical response (response according to RECIST 1.1 or stable disease with improvement of cutaneous lesions) in at least three patients. Exploratory objectives included histologic response (>30% decrease in Ki-67), FDG PET response, and β-receptor expression levels.
RESULTS: Fourteen patients were enrolled. The median duration of treatment was 26 days (range 21-42 days). The median highest propranolol dose was 160 mg/day (range 80 - 240 mg). Two patients showed clinical response (14%, 95% CI 3-100%). One of these patients showed a partial metabolic response on PET-CT. None of the tumors showed histologic response. The most common adverse event was grade 1/2 bradycardia (86%). There were no grade ≥ 3 adverse events. ADRB2 was overexpressed in 16 out of 18 tumors, in both responders and non-responders. None of the tumors showed ADRB1 overexpression.
CONCLUSIONS: This window-of-opportunity trial did not show clinical efficacy of propranolol monotherapy. However, two out of 14 patients did show clinical benefit. ADRB1/2 expression did not correlate with clinical response.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher\'s exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

UNASSIGNED: Radiation-induced sarcomas (RIS) tend to have aggressive behaviour and because of their rarity, the most appropriate management for these malignancies is uncertain.
UNASSIGNED: Using the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database, a national sarcoma registry, we aimed to investigate prognostic factors and outcomes for RIS.
UNASSIGNED: Retrospective study of RIS patients treated from 1996 to 2021 at three Canadian centres.
UNASSIGNED: RIS was defined as a sarcoma arising in a previously irradiated field following a 3+ year latency period, whose histology was distinct from the initially irradiated tumour. Clinicopathologic and treatment-related information was extracted from the CanSaRCC database. Overall survival (OS) was defined as the time from RIS diagnosis to death from any cause. Response rate (RR) to neoadjuvant chemotherapy (NACT) was based on physician assessment. Time-to-event analyses were estimated using the Kaplan-Meier method, with Cox regression for multivariate analysis. We considered a two-tailed p-value of <0.05 as statistically significant.
UNASSIGNED: One hundred seven tumours met the criteria for RIS and were divided into three subgroups: breast angiosarcoma (BAS, n = 54), osteosarcoma (OST, n = 16), and other soft-tissue sarcomas (STS, n = 37). Patients were mostly female (n = 85, 79%), treated initially for breast carcinomas (n = 54, 50.5%), and diagnosed with high-grade tumours (n = 61/71, 86%). None had evidence of synchronous metastasis. Patients with OST were younger (median age: 48 years, p < 0.001), and BAS had the shortest latency interval (8 versus 18 years for OST/STS, p < 0.001). Most patients underwent surgery, 76% (n = 76/100) R0; 24% (n = 26) received radiation therapy, mostly (n = 15, 57.7%) neoadjuvant. Among those receiving chemotherapy, 30 (75%) underwent NACT; among patients with documented response assessment, the RR was 68% (n = 17/25), being even higher in the BAS population (89.5%, n = 13/17). Median OS was 53 months (95% CI 34-101), with a 5-year OS of 47.6%; larger tumour size, high histologic grade and older age were independent prognostic factors for worse OS.
UNASSIGNED: Surgery is standard, and NACT might be useful to downsize large lesions, especially in BAS patients. Raising RIS awareness is fundamental to promoting appropriate management and fostering research through multi-institutional collaborations.

To test the antitumor effect and safety of peptide-based anticancer vaccination in dogs with hemangiosarcoma undergoing the standard of care (SOC; surgery and doxorubicin), canine hemangiosarcoma cells were infected with Salmonella typhi Ty21a to release immunogenic endoplasmic reticulum stress-related peptides into the extracellular milieu via CX43 hemichannels opening. The infected tumor cell secretome constituted the vaccine. Following the SOC, dogs with biologically aggressive hemangiosarcoma were vaccinated a total of five times, once every 3 weeks, and were followed up with serial imaging. A retrospective population of dogs undergoing the SOC alone served as controls. The primary endpoints were the time to progression (TTP) and overall survival (OS), and the secondary endpoints were toxicity and immune responses. A total of 28 dogs were vaccinated along with the SOC, and 32 received only the SOC. A tumor-specific humoral response along with a vaccine-specific T-cell response was observed. Toxicity did not occur. The TTP and OS were significantly longer in vaccinated versus unvaccinated dogs (TTP: 195 vs. 160 days, respectively; p = 0.001; OS: 276 vs. 175 days, respectively; p = 0.002). One-year survival rates were 35.7% and 6.3% for vaccinated and unvaccinated dogs, respectively. In dogs with hemangiosarcoma undergoing the SOC, the addition of a peptide-based vaccine increased the TTP and OS, while maintaining a safe profile. Moreover, vaccinated dogs developed a tumor-specific response, supporting the feasibility of future phase three studies.

Rare primary malignant bone sarcomas (RPMBS) account for 5%-10% of primary high-grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented.
Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high-grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m2 , ifosfamide 9 g/m2 , and cisplatin 90 mg/m2 ; postoperative methotrexate 8 g/m2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan-Meier curves, log-rank tests, and univariate Cox regression models were used.
In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40-66 years), and 67 patients were men. Eighty-eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty-three of 113 tumors were located in the extremities. Ninety-five of 113 patients presented with no evidence of metastases. After a median follow-up of 6.8 years (interquartile range [IQR], 3.5-9.8 years), the 5-year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%-77.5%), and it was 71.7% (IQR, 58.1%-81.6%) for patients with UPS and 54.9% (IQR, 29.5%-74.5%) for patients with leiomyosarcoma. Grade III-IV hematologic toxicity was reported in 81% patients; 23% had grade II-III neurotoxicity, and 37.5% had grade I-II nephrotoxicity. Five-year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities.
The survival of patients who had RPMBS in the current series was similar to that of age-matched patients who had high-grade osteosarcoma treated according to the same protocol. An osteosarcoma-like chemotherapy may be proposed in patients who have RPMBS.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

BACKGROUND: Cardiac sarcomas are rare and aggressive tumors with little known about the demographics, genetics, or treatment outcomes.
OBJECTIVE: The objectives of this study were to characterize the demographics, treatment modality, and survival associated with cardiac sarcomas and evaluate the potential for mutation-directed therapies.
METHODS: All cases from 2000 to 2018 of cardiac sarcoma were extracted from the SEER database. Genomic comparison utilized The Cancer Genome Atlas (TCGA) database, as well as reviews and re-analysis of past applicable genomic studies.
RESULTS: Cardiac sarcomas occurred most often in White patients, compared with national census data cardiac sarcomas occurred at a significantly higher rate in Asians. The majority of cases were undifferentiated (61.7%) and without distant metastases (71%). Surgery was the most common primary treatment modality and offered survival benefit (HR 0.391 (p = 0.001) that was most pronounced and sustained as compared to patients who received chemotherapy (HR 0.423 (p = 0.001) or radiation (HR 0.826 (p = 0.241) monotherapy. There was no difference in survival when stratified by race or sex; however, younger patients (< 50) had better survival. Genomics data on histologically undifferentiated cardiac sarcomas revealed a significant number were likely poorly differentiated pulmonary intimal sarcomas and angiosarcomas.
CONCLUSIONS: Cardiac sarcoma is a rare disease with surgery continuing to be a cornerstone of therapy followed by traditional chemotherapy. Case studies have indicated the potential for therapies directed to specific genetic aberrations to improve survival for these patients and utilization of next-generation sequencing (NGS) will help improve both classification and these therapies for cardiac sarcoma patients.

BACKGROUND: Breast angiosarcoma is a rare malignancy of endovascular origin, accounting for less than 1% of all mammary cancers. Our aim was to explore clinicopathological features and the factors associated with prognosis.
METHODS: We extracted information from the Surveillance, Epidemiology, and End Results Program (SEER) for all patients with breast angiosarcoma between 2004 and 2015. Chi-square analysis was used to compare the clinicopathological features in all patients. Overall survival (OS) was assessed using the Kaplan and Meier method. Univariate and multivariate analyses were performed to evaluate the factors associated with prognosis.
RESULTS: A total of 247 patients were included in the analyses. The median OS of patients with primary breast angiosarcoma (PBSA) and secondary breast angiosarcoma (SBAB) was 38 months and 42 months, respectively. The 1-, 3- and 5-year OS with PBSA was 80%, 39%, and 25%, respectively, and the 1-, 3- and 5-year OS with SBAB was 80%, 42%, and 34%, respectively. Multivariate analysis revealed that tumor size (p = 0.001), tumor grade (p < 0.001), tumor extension (p = 0.015), and tumor spread (p < 0.001) were statistically significant factors for OS. Partial mastectomy with radiation (HR = 0.160, 95% CI, 0.036-0.719, p = 0.016), partial mastectomy with chemotherapy (HR = 0.105, 95% CI, 0.011-1.015, p = 0.052), and partial mastectomy (HR = 0.125, 95% CI, 0.028-0.583, p = 0.007) were related to significantly better OS outcomes in primary angiosarcoma.
CONCLUSIONS: Primary breast angiosarcoma has a better clinical phenotype than secondary breast angiosarcoma. Although overall survival was not statistically significant, primary breast angiosarcoma was better than secondary breast angiosarcoma with systemic therapy. Depending on the outcome of survival, partial mastectomy is effective in treating primary breast angiosarcoma.

Angiosarcomas involving the liver can be hepatic primary or metastasis from another anatomic site, which have not been systematically compared. We analyzed a series of liver biopsy or resection specimens carrying a diagnosis of angiosarcoma collected between 2005 and 2022 at 3 tertiary medical centers. The cohort included 32 patients (20 M and 12 F) with a median age of 64 years. Nineteen were primary hepatic angiosarcoma (PHA) and 13 metastatic angiosarcoma to liver (MA). Males were predominant in PHA (15/19, 78%) compared to MA (5/13, 38%, P = .025). There was no age difference between the 2 groups. Five cases had background hepatic cirrhosis, which more likely harbored PHA (4/5, 80%). Multifocality and multiorgan involvement were common in both groups. Tumor size was significantly larger in PHA than in MA (10.4 versus 4.7 cm, P < .01). Histologically, there were no differences in terms of tumor morphology (spindled versus epithelioid) and growth patterns (vasoformative versus solid) between the 2 groups. Immunohistochemically, all tumor cells were positive for CD31 (28/28, 100%) and ERG (18/18, 100%). Molecular analysis in 5 cases demonstrated different mutation profiles involving different genes, including MTOR, PIK3CA, ARID1A, CDKN2A, PTEN, TP53, ATRX, KDR/VEGFR2, and so forth. On follow-up, 30 patients (93%) died of disease, with a median survival of 114 days. Univariate and multivariate analyses revealed PHA and epithelioid morphology to be associated with worse survival (P < .05), while treatment was associated with better survival (P < .001). Our results confirmed that angiosarcoma, particularly PHA, is extremely aggressive. Epithelioid morphology is an adverse prognosticator and may be used for tumor subclassification.