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Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed., Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US., Design, Setting, and Participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023., Main Outcomes and Measures: Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation., Results: The study included 19 289 patients (median age, 71 years [IQR, 59-80 years]; 10 506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1 000 000 person-years (95% CI, 3.1-3.5 cases per 1 000 000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1 000 000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13 955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001)., Conclusions and Relevance: This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.

Hepatic angiosarcoma is a rare, highly aggressive malignancy of the liver. The tumorigenesis of hepatic angiosarcoma has been relatively understudied in terms of aetiology and molecular properties. A recent study published in The Journal of Pathology revealed a strong association between hepatic angiosarcoma incidence and chronic kidney disease, particularly in end-stage renal disease using population-based data from the National Health Insurance Research Database in Taiwan and an institutional cohort. The study also revealed enrichment in the mutational signature of aristolochic acid exposure and is the first reported observation of this mutational signature in human sarcomas. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Purpose: Sarcomas are a heterogeneous group of malignant neoplasms with a wide range of histological types and occur in almost any anatomic site and side. This study evaluated the prognostic factors in sarcoma patients based on German clinical cancer registry data., Methods: The German clinical cancer register of Saxony-Anhalt was used for all data analyses. Sarcoma cases of all clinical or pathological T-stages (T1a-T4c), all N-stages (N0-3) and M-stages (0-1b) corresponding to the Union for International Cancer Control (UICC) stages I to IVB were considered. In our analyses, 787 cases diagnosed between 2005 and 2022 were included. Further, we assessed the association of cancer-related parameters with mortality and hazard ratios (HR) from the Cox proportional hazard models. We included sex, age at diagnosis, histological grade, T-, N- and M-stages, tumor size, tumor localization and tumor side as parameters in our regression models., Results: The majority of sarcoma patients were diagnosed with leiomyosarcoma (12%), liposarcoma (11%), angiosarcoma (5.3%) and myxofibrosarcoma (2.7%). In our univariate regression models, tumors localized in more than one location, head, face and neck region as well as the pelvis and lower extremity were associated with increased mortality risk (more than one location: HR 7.10, 95% CI 2.20-22.9; head, face and neck: HR 1.35, 95% CI 0.89-2.06; pelvis: HR 1.27, 95% CI 0.86-1.89; lower extremity: HR 1.44, 95% CI 1.05-1.96). Higher histological grades, UICC-grades and TNM-stages were related to a higher mortality risk. Differing histological subtypes had significant influence on overall survival and progression-free survival. Patients diagnosed with fibromyxoid sarcoma, rhabdomyosarcoma and angiosarcoma were related to higher mortality risk compared to other histological subtypes (fibromyxoid sarcoma: HR 5.2, 95% CI 0.71-38.1; rhabdomyosarcoma: HR 2.93, 95% CI 1.44-6.00; angiosarcoma: HR 1.07, 95% CI 0.53-2.18)., Conclusions: Histological grade, tumor size, nodal and distant metastasis, tumor localization and histological subtype were determined as prognostic factors in terms of survival., (© 2023. The Author(s).)

Objectives: Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment., Methods: Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival., Results: Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11)., Conclusions: We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma., Competing Interests: E.T.L.—Clinical trial funding from BioAtla, Ayala, and SpringWorks. L.D.C.—Clinical trial funding from Eli Lilly, AADi, BluePrint Medicine, Iterion, Gradalis, Philogen, Advenchen Laboratories, and CBA Pharma. Honoraria or has served on advisory boards for Daaichi Sankyo. M.J.W.—Clinical trial support from Deciphera, Adaptimmune, GSK, Athenex, Foghorn Therapeutics, Shaqsi, Presage Biosciences, Inhibrx, and Incyte. Consulting fees from Adaptimmune, Epizyme, Aadi, and Deciphera. H.M.L.—Research funding from Tolmar, EliLilly, GE Healthcare, Sanofi, and Zymeworks. Consulting for GE Healthcare, Novartis, Sanofi, and Eli Lilly. J.M.S.—Research funding from Celcuity, Genentech, Xencor, Pfizer, SeaGen, Merck, Carisma, and Lyell. Consultant/advisory boards: A2 Biotherapeutics, Volastra Therapeutics, GE Healthcare, Sensei Therapeutics, and GlaxoSmithKline. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Haemangiosarcoma is a relatively common malignant tumour in dogs, and one of the primary outcomes of interest for the Golden Retriever Lifetime Study. This study collects longitudinal data and samples from a cohort of golden retrievers, with the aim of identification of nutritional, genetic, environmental, lifestyle and reproductive risk factors for cancers and other important diseases in dogs. This analysis describes the accumulating data and samples, which are available for use by researchers to fulfil the study's objectives. As of September 2022, 233/3044 dogs enrolled in the study had been diagnosed with haemangiosarcoma (7.65%), with an incidence rate of 1.10 cases per 100 dog-years. Visceral haemangiosarcoma was the most common, affecting 211/3044 study dogs (6.9%). One hundred and twenty eight visceral haemangiosarcoma diagnoses specified the presence of splenic tumours (60.7%) and 119 specified the presence of cardiac tumours (56.4%). The probability of remaining without a haemangiosarcoma diagnosis declined from 100% from approximately 4 years of age, to a 12 year probability of 91.1% in intact females (95% CI 84.4%-98.3%), 60.7% in neutered females (95% CI 41.6%-88.6%), 72.9% in intact males (95% CI 62.9%-84.6%) and 70.0% in neutered males (95% CI 53.4%-92.0%). The 1 year survival probability for visceral haemangiosarcoma was 1.42% (95% CI 0.37%-5.47%); for cutaneous haemangiosarcoma, it was 84.6% (95% CI 67.1%-99.99%). The accumulated data and samples are a considerable resource for further investigation of canine haemangiosarcoma and have a potential role in translational medicine., (© 2023 John Wiley & Sons Ltd.)

Background: Breast angiosarcoma is a rare disease mostly observed in breast cancer (BC) patients who have previously received radiotherapy (RT). Little is known about angiosarcoma aetiology, management, and outcome. The study aim was to estimate risk and to characterize breast angiosarcoma in a Swedish population-based cohort., Methods: The Swedish Cancer Registry was searched for breast angiosarcoma between 1992 and 2018 in three Swedish healthcare regions (population 5.5 million). Information on previous BC, RT, management, and outcome were retrieved from medical records., Results: Overall, 49 angiosarcomas located in the breast, chest wall, or axilla were identified, 8 primary and 41 secondary to BC treatment. Median age was 51 and 73 years, respectively. The minimum latency period of secondary angiosarcoma after a BC diagnosis was 4 years (range 4-21 years). The cumulative incidence of angiosarcoma after breast RT increased continuously, reaching 1.4‰ after 20 years. Among 44 women with angiosarcoma treated by surgery, 29 developed subsequent local recurrence. Median recurrence-free survival was 3.4 and 1.8 years for primary and secondary angiosarcoma, respectively. The 5-year overall survival probability for the whole cohort was 50 per cent (95 per cent c.i., 21 per cent-100 per cent) for primary breast angiosarcoma and 35 per cent (95 per cent c.i., 23 per cent-54 per cent) for secondary angiosarcoma., Conclusion: Breast angiosarcoma is a rare disease strongly associated with a history of previous BC RT. Overall survival is poor with high rates of local recurrences and distant metastasis., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored with respect to its etiology and mutational landscapes. To clarify the association between HAS and end-stage renal disease (ESRD), we used nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including nine ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked second among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort confirmed CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, p < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, p = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, p < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from exposure to aristolochic acid or related compounds. A high TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

Background: Soft tissue sarcoma is a rare but serious side-effect of radiotherapy to treat breast cancer, and rates are increasing in the USA. We evaluated potential co-factors in two complimentary cohorts of US breast cancer survivors., Methods: In this retrospective cohort study, we sourced data from the Kaiser Permanente (KP) cohort and the Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort, both in the USA. The KP cohort included 15 940 women diagnosed with breast cancer from Jan 1, 1990, to Dec 31, 2016, in KP Colorado, KP Northwest (which serves Oregon and Southwest Washington state), or KP Washington, with detailed treatment data and comorbidities (including hypertension and diabetes at or before breast cancer diagnosis) from electronic medical records. The SEER cohort included 457 300 women diagnosed with breast cancer from Jan 1, 1992, to Dec 31, 2016, within the 13 SEER registries across the USA, with initial treatment data (yes vs no or unknown). Eligibility criteria in both cohorts were female breast cancer survivors (stage I-III) aged 20-84 years at diagnosis who had breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis. The outcome of interest was any second thoracic soft tissue sarcoma (angiosarcomas and other subtypes) that developed at least 1 year after breast cancer diagnosis. Risk factors for thoracic soft tissue sarcoma were assessed using multivariable Poisson regression models., Findings: In the KP cohort, median follow-up was 9·3 years (IQR 5·7-13·9) and 19 (0·1%) of 15 940 eligible, evaluable women developed a thoracic soft tissue sarcoma (11 angiosarcomas, eight other subtypes). Most (94·7%; 18 of 19) thoracic soft tissue sarcomas occurred in women treated with radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (relative risk [RR] 8·1 [95% CI 1·1-60·4]; p=0·0052), but there was no association with prescribed dose, fractionation, or boost. The RR of angiosarcoma after anthracyclines was 3·6 (95% CI 1·0-13·3; p=0·058). Alkylating agents were associated with an increased risk of developing other sarcomas (RR 7·7 [95% CI 1·2-150·8]; p=0·026). History of hypertension (RR 4·8 [95% CI 1·3-17·6]; p=0·017) and diabetes (5·3 [1·4-20·8]; p=0·036) were each associated with around a five-times increased risk of angiosarcoma. In the SEER cohort, 430 (0·1%) of 457 300 patients had subsequent thoracic soft tissue sarcomas (268 angiosarcomas and 162 other subtypes) after a median follow-up of 8·3 years (IQR 4·3-13·9). Most (77·9%; 335 of 430) cases occurred after radiotherapy; thus, radiotherapy was associated with a significantly increased risk of developing a thoracic soft tissue sarcoma (RR 3·0 [95% CI 2·4-3·8]; p&lt;0·0001) and, for angiosarcomas, the RR for breast-conserving surgery plus radiotherapy versus mastectomy plus radiotherapy was 1·9 (1·1-3·3; p=0·012). By 10 years after radiotherapy, the cumulative incidence of thoracic soft tissue sarcoma was 0·21% (95% CI 0·12-0·34) in the KP cohort and 0·15% (95% CI 0·13-0·17) in SEER., Interpretation: Radiotherapy was the strongest risk factor for thoracic soft tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance., Funding: US National Cancer Institute and National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The current study aimed to investigate the prognosis and treatment of primary cutaneous angiosarcoma (PCA) and primary subcutaneous angiosarcoma (PSCA), and tried to develop a prognostic nomogram model of them., Methods: A total of 1763 cases retrieved from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. Survival analyses were performed to explore the prognosis of patients and the effects of different treatment methods. All data were randomly allocated into a training set and a testing set to develop and validate the nomogram model., Results: The findings showed that age, sex, grade, tumor size, multiple primary malignant tumors, stage, primary site surgery (PSS), radiotherapy (RT), and chemotherapy (CT) were correlated with prognosis ( p  < .05). The nomogram achieved good accuracy in predicting the prognosis. PSS + RT + CT showed the best prognosis for patients in stages I, II, and III ( p  < .05)., Conclusion: PCA and PSCA are rare with poor prognoses. Patients undergoing PSS may not gain survival benefits from combining with RT or (and) CT, whereas PSS + RT + CT should be actively performed in earlier stages to improve the prognosis of patients. The nomogram model can be used to predict the overall survival rate and guide better treatment.

Introduction: Despite the significant clinical importance of sex among factors affecting cancer progression and survival, it remains one of the least studied factors. Therefore, we sought to examine these differences in relation to primary malignant cardiac tumors (PMCTs) using a national data set., Methods: The 2004-2017 National Cancer Database was queried for patients with PMCTs. Annual trend of females' percent was assessed. Overall survival predictors were evaluated with Kaplan-Meier and Cox-regression. Subgroup analysis was done based on histology, comorbidity index, race, insurance, and surgical treatment., Results: PMCTs were identified in 736 patients (median age 52, female [47.8%]). Most of them were high-grade (49.2%). About 60% underwent surgery. Angiosarcoma (43%), fibrosarcoma (5.2%), and leiomyosarcoma (5.2%) were the most common pathologies. Based on multivariate Cox-regression, higher income, higher comorbidity index, angiosarcoma, and Stage III/IV were associated with higher late mortality, while year of diagnosis and use of surgery or chemotherapy were associated with lower mortality. Among the surgical group, age, higher income, higher comorbidity index, angiosarcoma, and Stage III/IV were independent predictors of higher late mortality, while private insurance and year of diagnosis were associated with lower late mortality. No difference was seen between males and females in 30-day and late mortality (p = .71). Subgroup analysis based on Cox-regression showed no differences in late mortality between males and females., Conclusion: PMCTs have poor overall survival. Surgery and chemotherapy were associated with longer survival benefits. On the contrary, the associated risk factors for mortality were advanced age, higher comorbidity index, angiosarcoma histology, and Stage III/IV., (© 2022 Wiley Periodicals LLC.)

Abstract: Primary splenic cancers represent a small number of cancer cases and studies on its clinicopathological features and outcomes are limited. Splenic lymphomas and primary splenic angiosarcoma (PSA) are the 2 most common histological types of splenic cancers. This population-based study aimed to investigate the clinical characteristics and survival outcomes of patients with splenic lymphomas or PSA.Patients diagnosed with splenic lymphomas or PSA between 2000 and 2015 were identified from the Surveillance Epidemiology and End Results database of the National Cancer Institutes. Overall survival (OS) and cancer-specific survival (CSS) rates were calculated using the Kaplan-Meier method. A Cox proportional hazard models were used to identify independent predictors of cancer-specific mortality.A total of 700 patients with splenic lymphoma and 48 patients with PSA were included in this study. The median age of patients with splenic lymphoma was 65 years and 57 years for patients with PSA. For patients with splenic lymphoma, the most prevalent histological subtypes were splenic marginal zone lymphoma and diffuse large B-cell lymphoma. A total of 52.6% of the cases had stage IV disease based on the Ann Arbor staging system. Five-year OS and CSS were 76.9% and 83.4%, respectively. Multivariate analysis revealed that independent predictors of splenic lymphoma CSS included race, stage, chemotherapy, and histological subtype. However, a much shorter OS time was seen in the PSA cohort which had a 5-year OS of 11.8%, a median OS of 10.0 months and the 5-year CSS of 12.4%. Chemotherapy was correlated with better outcomes in patients with PSA. However, the survival benefits of surgery for splenic cancer were not statistically significant in our study.The current study is the largest cohort of primary splenic cancer presented in literature based on the Surveillance Epidemiology and End Results database and our large series describe the characteristics and survival outcomes of such rare diseases which may provide reliable information for further studies and clinicians., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Angiosarcoma developing in chronically lymphedematous tissue, or Stewart-Treves syndrome (STS), is a rare and lethal complication of lymphedema. This systematic review summarizes characteristics and outcomes of STS and other cutaneous malignancies arising in chronic lymphedema., Methods: MEDLINE and EMBASE databases were searched on February 19th, 2021, to identify 200 articles included in the analysis., Results: Of 369 included patients, 89.7% (n = 331/369) had STS and 10.3% (n = 38/369) had other associated malignancies. Mean age of onset was 61.2 years, and 85.9% (n = 317/369) of cases were female. Common risk factors were previous cancer history (69.8%, n = 258/369) and radiation history (53.7%, n = 198/369). Lymphedema was most commonly attributed to surgical causes (68.3%, n = 252/369). STS begins on average 14.9 years after lymphedema with mortality of 53.9% (n = 178/331) and remission rate of 16.1% (n = 53/331). Other malignancies begin on average 23.7 years after lymphedema, with mortality of 10.5% (n = 4/38) and remission rate of 31.6% (n = 12/38). STS and other malignancies had 5-year survivals of 22.4% and 65.2%, respectively (P = 0.00145). For all patients, patients initially treated with excision had the best survival (median: 48 months, 5-year survival: 43.3%) and radiotherapy had the worst survival (median: 10 months, 5-year survival: 6.5%) (P = 0.0141)., Conclusion: Malignancy can appear in lymphedematous tissue many years after lymphedema onset. STS has poorer prognosis compared to other malignancies. Further research should be conducted to better understand the causes, risk factors, and management of this phenomenon., (© 2021 the International Society of Dermatology.)

Background: Malignant vascular tumors (MVTs) are rare and often misdiagnosed due to wide range of clinical presentations, varied histology, and exquisite imagining features. We aim to characterize two different types of MVTs of the liver: hepatic angiosarcomas (HA) and hepatic epithelioid hemangioendotheliomas (HEHE)., Methods: Data on HA and HEHE between 1975 and 2016 were extracted from the SEER database and analyzed., Results: A total of 366 patients with HA were identified where 64.2% were male and 79% of White race. The median age at diagnosis was 64 ± 16.2 years. Distant metastasis was found in 24% of patients, regional disease in 22.1%, and localized disease in 21.3%. The median overall survival for HA was 2 months. For HEHE, 120 cases were identified, 32.5% were male and 80% of White race. The median age of diagnosis was 51 ± 16.8 years. Distant metastasis was found in 37.5% of patients, regional disease in 27.5%, and localized disease in 20%. The median overall survival was 182 months., Conclusion: Patients' demographics such as race, age, and gender may assist in elucidating distinct subtypes of MVTs. HA is an aggressive tumor despite intervention. Patients with HEHE tumors have significantly better survival compared to patients with HA. Further studies are needed to deepen our knowledge about the histopathology of these tumors, the outcomes of liver transplantation as a therapeutic alternative, and available molecular targets for MVTs., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Angiosarcoma of the breast is rare and aggressive. It can occur as a de novo tumor or secondary to breast cancer treatment. The purpose of this study is to analyze differences between patients with primary and secondary angiosarcoma of the breast and investigate potential risk factors for its development., Patients and Methods: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute database was queried to identify patients with angiosarcoma of the breast, trunk, shoulder, and upper arm. The population-based incidence was analyzed. Primary and secondary angiosarcoma cases were identified and compared. Breast cancer characteristics of secondary angiosarcoma patients were compared with all breast cancer patients in the database who did not develop angiosarcoma., Results: Overall, 904 patients were included, and 65.4% were secondary angiosarcomas. These patients had worse survival, were older, more likely to be White, more likely to have regionally advanced disease, and had angiosarcoma tumors of higher pathologic grade. Independent factors associated with development of secondary angiosarcoma among breast cancer patients included White race, older age, invasive tumor, lymph node removal, lumpectomy, radiation treatment, and left-sided tumor. Although the mean time to develop angiosarcoma after breast cancer diagnosis was 8.2 years, the risk continues to increase up to 30 years after breast cancer treatment., Conclusion: Angiosarcoma is rare but increasing in incidence. Secondary angiosarcomas are more common and exhibit more aggressive behavior. Several factors for angiosarcoma after breast cancer treatment could be identified, which may help us counsel and identify patients at risk., (© 2021. Society of Surgical Oncology.)

Background: High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics., Methods: Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, n = 15) and VC exposure-matched controls ( n = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed., Results: Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling., Conclusions: The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.

Background: Breast angiosarcomas are rare tumours of vascular origin. Secondary angiosarcoma occurs following radiotherapy for breast cancer. Angiosarcomas have high recurrence and poor survival rates. This is concerning owing to the increasing use of adjuvant radiotherapy for the treatment of invasive breast cancer and ductal cancer in situ (DCIS), which could explain the rising incidence of angiosarcoma. Outcome data are limited and provide a poor evidence base for treatment. This paper presents a national, trainee-led, retrospective, multicentre study of a large angiosarcoma cohort., Methods: Data for patients with a diagnosis of breast/chest wall angiosarcoma between 2000 and 2015 were collected retrospectively from 15 centres., Results: The cohort included 183 patients with 34 primary and 149 secondary angiosarcomas. Median latency from breast cancer to secondary angiosarcoma was 6 years. Only 78.9 per cent of patients were discussed at a sarcoma multidisciplinary team meeting. Rates of recurrence were high with 14 of 28 (50 per cent ) recurrences in patients with primary and 80 of 124 (64.5 per cent ) in those with secondary angiosarcoma at 5 years. Many patients had multiple recurrences: total of 94 recurrences in 162 patients (58.0 per cent). Median survival was 5 (range 0-16) years for patients with primary and 5 (0-15) years for those with secondary angiosarcoma. Development of secondary angiosarcoma had a negative impact on predicted breast cancer survival, with a median 10-year PREDICT prognostic rate of 69.6 per cent, compared with 54.0 per cent in the observed cohort., Conclusion: A detrimental impact of secondary angiosarcoma on breast cancer survival has been demonstrated. Although not statistically significant, almost all excess deaths were attributable to angiosarcoma. The increased use of adjuvant radiotherapy to treat low-risk breast cancer and DCIS is a cause for concern and warrants further study., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature., Patients and Methods: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature., Results, Conclusion: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the epidemiological data, prognostic factors, and treatment outcomes of bone angiosarcoma (BA)., Methods: This retrospective study was based on the Surveillance, Epidemiology, and End Results (SEER) database. The medical records of BA patients were selected from the SEER database from 1975 to 2016. Variables including patients' baseline demographics (age, sex, marital status, and year of diagnosis), tumor characteristics (tumor size, grade, and SEER Historic Stage A), and treatment (surgery and radiotherapy) were selected for further analysis. The research endpoints were overall survival (OS) and cancer-specific survival (CSS). The optimal cutoff values of continuous variables including age, year of diagnosis, and tumor size were identified using the X-tail program. Univariate Cox regression was used to identify potential prognostic factors and multivariate Cox regression was used to identify independent prognostic factors. All prognostic factors were included to predict the survival time compared to the median OS and CSS times via the novel nomograms. To validate the internal validation of nomograms, we analyzed the concordance indices (C-index)., Results: This study enrolled a total of 271 patients with malignant vascular bone tumors among residents of the United States between 1975 and 2016. After applying the exclusion criteria (one case without active follow-up), this study included 152 patients with BA. The median survival time of BA was significantly shorter than that of malignant vascular bone tumors for OS (9 months vs 27 months, P < 0.001). Age, year of diagnosis, tumor size, grade, stage, and surgery were identified as potential prognostic factors for OS or CSS in univariate Cox regression. However, only age (P < 0.001, P < 0.001), stage (P = 0.002, P < 0.001), and surgery (P = 0.001, P = 0.002) were independent prognostic factors for CSS and OS, respectively, in the multivariate analysis. Younger patients less than 54 years have significantly better prognosis for CSS/OS than patients between 54 and 67 years (Hazard ratios [HRs]: 1.651 [1.763-3.575], 2.557 [1.395-4.687]) and more than 67 years (HRs: 4.404 [2.237-8.670], 5.113 [2.923-8.942]). For CSS/OS, the survival time of patients with localized stage was significantly longer than that of patients with regional stage (HRs: 1.530 [0.725-3.228], 1.548 [0.834-2.873]) and that of patients with distant stage (HRs: 1.706 [0.899-3.237], 2.101 [1.254-3.520]). Patients with surgery had more survival time than patients without surgery for CSS/OS (HRs: 2.861 [1.542-5.310], 2.103 [1.308-3.379]). All factors were further included to generate nomograms for CSS and OS. The C-indexes for the internal validation of OS and CSS prediction were 0.787 (95% confidence interval [CI]: 0.738-0.836) and 0.768 (95% CI: 0.717-0.819), respectively., Conclusions: Age, stage, and surgery were closely associated with prognosis in patients with BA, and this clinical model was a favorable tool to evaluate survival possibilities., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Haemoperitoneum secondary to ruptured splenic tumours can be either benign or malignant in origin. The majority of previous studies of canine haemoperitoneum have been retrospective, which are associated with well-recognized biases, such as the potential to underappreciate the diversity of outcomes in a complex presentation such as haemoperitoneum. This study seeks to prospectively define perioperative morbidity and mortality of haemoperitoneum in dogs secondary to ruptured splenic masses. Forty dogs with haemoperitoneum secondary to a ruptured splenic mass met the inclusion criteria. As expected, the cohort predominately consisted of older large breed dogs. All dogs underwent preoperative staging and had a splenectomy performed. Histopathologic analysis was performed on the splenic mass, as well as any possible metastatic lesions that were noted intra-operatively. Perioperative care outside of splenectomy was delivered in specialty practices using current conventional approaches to care (eg, transfusions and anti-arrhythmic medications). Fifteen dogs (37.5%) had benign splenic tumours and were cured with surgery alone, whereas 62.5% had malignant disease (most often haemangiosarcoma [HSA]). Surgical outcomes were highly favourable in the vast majority of dogs. Indeed, 38 dogs (95%) survived and were discharged after a median hospitalization of 39.5 hours. Independent predictors of longer hospitalization times included receiving a transfusion and the development of an arrhythmia. Although small, this cohort defines distinctive and optimistic perspectives for dogs with haemoperitoneum from splenic tumour rupture. These favourable outcomes from this prospective study are sufficient to ask if larger prospective studies should be conducted to better inform owners during this challenging cancer emergency presentation., (© 2020 John Wiley & Sons Ltd.)

Background: Cutaneous angiosarcoma (CAS) is a rare, malignant tumor of vascular mesenchymal origin accounting for less than 1% of all sarcomas., Objective: To examine epidemiologic trends and outcomes in CAS., Methods: In this retrospective, population-based study, patients with CAS were identified from the Surveillance Epidemiology and End Results database. Age, sex, and race-standardized incidence rates (IRs) were calculated. Survival was assessed with Kaplan-Meier curves and Cox proportional hazards models., Results: Of 811 patients with CAS, 43% had a prior primary cancer. CAS IR for patients without prior primary cancers dropped from 5.88 per 100,000 in 1973 to 1984 to 2.87 per 100,000 in 2005 to 2014. In those with prior primary cancers, IR rose from 0.03 per 100,000 in 1973 to 1984 to 2.25 per 100,000 in 2005 to 2014. On multivariate analysis, patients older than 70 years of age had a higher risk of death compared with those younger than 50 years (hazard ratio, 2.16; 95% confidence interval 1.33-3.57; P = .002), and distant disease was associated with increased risk of death compared with localized disease (hazard ratio, 1.50; 95% confidence interval, 1.11-2.03; P = .008). Receipt of surgery and/or radiation therapy was not associated with survival., Limitations: Potential selection and miscoding bias, retrospective nature., Conclusion: CAS rates are rising among those with other prior primary cancers. Survival is not affected by current therapeutic strategies, highlighting the need for additional treatment options., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The genetic and breed susceptibility of visceral hemangiosarcoma in dogs has been studied, but there is no evidence of environmental risk factors as reported in human medicine. We conducted a case-control study in which the sampling population was the list of canine oncology cases of the Animal Tumour Registry of Lazio region, Italy (2009-2017). We defined cases as dogs with visceral hemangiosarcoma and controls as dogs affected by another neoplasm. The ratio between controls and cases was 3:1. Analysed variables were: age, weight, sex, reproductive status, size, breed, nutrition habit, living environment and location of the house. We performed a preliminary univariate analysis to select potential risk factors (p-value < 0.2) then entered in a forward stepwise logistic regression model. Ninety-three cases enrolled in the study were compared with 279 controls. The multivariable logistic regression identified age, reproductive status and breed as significant risk factors. Results showed an increasing risk with increasing age for age classes 6-10 and > 10 years old (OR = 9.69, 95 % CI: 1.21-77.62; OR = 14.01, 95 % CI: 1.65-119.03). Neutered animals (male and female) were at greater risk compared to intact ones. The breeds at greatest risk were German shepherd (OR = 4.17, 95 % CI: 1.25-13.86) and mixed breed (OR = 3.50, 95 % CI: 1.44-8.51). The last finding could be explained by the genetic origin of the animals, which may include German shepherd or another possible breed at risk. No other individual or environmental variables were identified as risk factors. The findings of this work indicate that genetic predisposition is the key element in visceral hemangiosarcoma development., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The hypothesis that neutered dogs in the Veterinary Medical Database (VMDB) are at increased risk for developing hemangiosarcoma (HSA) was tested. Dogs ( n = 5736) were diagnosed with HSA from a population of 2 106 324 dogs in the VMDB from 1964 to 2003. A case-control design matched on age and time period was created for general, cardiac, and splenic HSAs. A logistic regression analysis was performed including breed. Spayed females had an odds ratio (OR) of 1.59 for splenic, 1.47 for cardiac, and 1.72 for HSA in general. Castrated males had an OR of 1.26 for splenic and 1.14 for HSA in general compared to intact males. Controlled for historical time period and patient age, VMDB data support that neutering is associated with development of splenic HSA and HSA in general in both male and female dogs, but not cardiac HSA with an apparently lower than previously described magnitude of association. Key clinical message: This case-control design confirms an association between neutering and development of HSA and splenic HSA, but not cardiac HSA, in both male and female dogs. By controlling for time period at diagnosis, the bias of recent early neuter practices is eliminated, suggesting early neuter is not a principal driver of this effect., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Hemangiosarcoma (HSA), a locally invasive and highly metastatic endothelial cell neoplasm, accounts for two-thirds of all cardiac and splenic neoplasms in dogs. Bartonella spp. infection has been reported in association with neoplastic and non-neoplastic vasoproliferative lesions in animals and humans. The objective of this study was to determine the prevalence of Bartonella spp. in conjunction with two other hemotropic pathogens, Babesia spp. and hemotropic Mycoplasma spp., in tissues and blood samples from 110 dogs with histopathologically diagnosed HSA from throughout the United States. This was a retrospective, observational study using clinical specimens from 110 dogs with HSA banked by the biospecimen repository of the Canine Comparative Oncology and Genomics Consortium. Samples provided for this study from each dog included: fresh frozen HSA tumor tissue (available from n = 100 of the 110 dogs), fresh frozen non-tumor tissue (n = 104), and whole blood and serum samples (n = 108 and 107 respectively). Blood and tissues were tested by qPCR for Bartonella, hemotropic Mycoplasma, and Babesia spp. DNA; serum was tested for Bartonella spp. antibodies. Bartonella spp. DNA was amplified and sequenced from 73% of dogs with HSA (80/110). In contrast, hemotropic Mycoplasma spp. DNA was amplified from a significantly smaller proportion (5%, p<0.0001) and Babesia spp. DNA was not amplified from any dog. Of the 100 HSA tumor samples submitted, 34% were Bartonella PCR positive (32% of splenic tumors, 57% of cardiac tumors, and 17% of other tumor locations). Of 104 non-tumor tissues, 63% were Bartonella PCR positive (56% of spleen samples, 93% of cardiac samples, and 63% of skin/subcutaneous samples). Of dogs with Bartonella positive HSA tumor, 76% were also positive in non-tumor tissue. Bartonella spp. DNA was not PCR amplified from whole blood. This study documented a high prevalence of Bartonella spp. DNA in dogs with HSA from geographically diverse regions of the United States. While 73% of all tissue samples from these dogs were PCR positive for Bartonella DNA, none of the blood samples were, indicating that whole blood samples do not reflect tissue presence of this pathogen. Future studies are needed to further investigate the role of Bartonella spp. in the development of HSA., Competing Interests: In conjunction with Dr. Sushama Sontakke and North Carolina State University, Edward B. Breitschwerdt, DVM holds U.S. Patent No. 7,115,385: “Media and Methods for Cultivation of Microorganisms”, which was issued October 3, 2006. He is a co-founder, shareholder and Chief Scientific Officer for Galaxy Diagnostics, a company that provides advanced diagnostic testing for the detection of Bartonella species infections. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare no potential conflicts of interest.

Objective: Limited by sample size, angiosarcoma was rarely studied. We aimed to investigate the characteristics and prognosis of angiosarcoma in the National Cancer Institute's Surveillance, Epidemiology and End Results database., Methods: Patients who were diagnosed with primary angiosarcoma from 1973 to 2014 were extracted from the Surveillance, Epidemiology and End Results database. Kaplan-Meier analysis was used to estimate the overall survival, and the difference between groups was tested by the log-rank test. Multivariate Cox regression analyses were employed to identify prognostic factors for primary angiosarcoma., Results: A total of 4537 patients with angiosarcoma were included with the median age of 69 years. The median overall survival was 82.1 (95% confidence interval: 76.5-87.7) months. Overall 1-, 2- and 5-year survival rates were 55.2 ± 0.7, 41.0 ± 0.7 and 26.3 ± 0.7%, respectively. In the univariate analysis, age, gender, marital status, race, primary site, tumor grade, tumor size, Surveillance, Epidemiology and End Results historic stage and the surgery of primary site were significantly associated with overall survival. Multivariate Cox regression showed that factors including the patients older than 69 years, male, unmarried status, other primary sites, grades (III and IV), tumor size ≥ 5 cm, regional and distant stage and non-surgery were independently associated with poor survival. The results were consistent after excluding the patients in IV stages., Conclusions: This large population-based study comprehensively described the survival rate and prognostic factors for angiosarcoma in the United States. Age, gender, marital status, primary sites, tumor grade and size and historic stage were determinants of survival, and surgery can improve the prognosis of patients with angiosarcoma., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Portal hypertension, liver fibrosis, and angiosarcoma of the liver (ASL) have been reported among workers exposed to vinyl chloride monomer (VCM) since the 1970s. In 2007, the International Agency for Research on Cancer established the association of VCM with hepatocellular carcinoma (HCC), though only on the basis of the few cases available. Thereafter, recent reports from the United States cohort and a European sub-cohort of vinyl chloride workers provided compelling evidence of a strong association between cumulative VCM exposure and HCC risk. Further areas of research include the risk of liver cancer at lower levels of exposure and different patterns of risk of ASL and HCC with the time since exposure. The evidence of interaction between VCM exposure and other known liver carcinogens such as alcohol and chronic viral infection provides clues for the health surveillance of exposed workers. Notably, also the risk of VCM-associated chronic liver disease is modulated by alcohol consumption, viral infection, and genetic polymorphism. A counter-intuitive finding from cohort studies of exposed workers is the lower mortality from liver cirrhosis with respect to the general population; this can be attributed to the healthy worker effect and to the selection of liver cancer as the cause of death in the presence of concomitant chronic liver disease. Studies designed to overcome these intricacies confirmed an association between cumulative VCM exposure and the risk of liver cirrhosis., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.

Histiocytic sarcoma (HS) and hemangiosarcoma (HSA) are uncommon and aggressive neoplasms that develop much more frequently in dogs than in cats. Breed-specific predispositions have been identified for both cancers. The development of novel diagnostics is underway and may aid in earlier diagnosis. Therapeutic approaches to HS and HSA depend on the stage of disease and may include surgery, radiation therapy, and chemotherapy. Such interventions improve outcome; however, aside from a small number of clinical circumstances, both diseases are considered largely incurable. Continued efforts toward the identification of driver mutations and subsequent druggable targets may lead to improvements in long-term prognosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Primary cardiac angiosarcoma (PCAS) is a rare type of tumour. Furthermore, descriptions of the demographic features and prognostic factors of PCAS patients have been poorly reported., Methods: A population cohort study was conducted using retrospectively extracted data from the SEER (Surveillance, Epidemiology and End Results) database for patients with histological diagnoses of PCAS; the extracted information included demographic, treatment and outcome data., Results: A total of 168 cases of PCAS from 1973 to 2013 were included. The mean age at diagnosis was 44.4 ± 15.5 years. PCAS was more prevalent in men than in women. The majority of PCAS patients were white (67.3%), while the incidence of PCAS in black individuals was relatively infrequent (19.0%). In addition, 87 cases were classified as distant stage, 44 as regional stage, and 33 as localized stage. The median disease-specific survival (DSS) was 7.22 months, and the 1-, 2- and 5-year DSS rate for PCAS patients was 34.7%, 14.3% and 10.2%, respectively. Further multivariate analyses showed that an age at (greater than or equal to) 45 years (HR 2.165), no radiotherapy (HR 1.629), tumour size > 5 cm (HR 3.182), and the summary stage was associated with worse PCAS-related survival. Cancer-directed surgery and radiotherapy significantly improved the DSS for patients with PCAS (P < 0.05). The C-index of the nomograms was 0.706 (95% CI 0.654-0.758), and the calibration curves showed good agreement between the nomogram prediction and actual observation., Conclusion: PCAS is a rare cancer that is prone to have poor prognoses. To understand PCAS more thoroughly, more cases with adequate information are needed.

Various splenic diseases can result in a splenic mass and necessitate splenectomy. The objective of this study was to compare the prevalence of malignant and benign splenic diseases, and type of malignant disease, in dogs categorised by breed size. It was hypothesised that the prevalence of splenic disease would be significantly different in small versus large-breed dogs. All dogs had a splenic mass identified with ultrasonography or CT, and had a confirmed diagnosis. Dogs were categorised as small, medium and large breeds according to breed standards. There were 54 small, 139 medium and 41 large-breed dogs; 129/234, 55% (95% CI 49% to 61%) had malignant disease versus 105/234, 45% (95% CI 39% to 51%) with benign disease (P=0.117). The prevalence of malignant versus benign disease was not significantly different for small (P=0.276), medium (P=0.074) or large-breed dogs (P=0.080). Small-breed dogs were 2.3 times more likely than large-breed dogs to have benign disease. Small-breed dogs with malignant disease were one-third as likely as large-breed dogs to have haemangiosarcoma. In conclusion, the overall prevalence of malignant and benign diseases was 50:50; however, compared with large-breed dogs, small-breed dogs are more likely to have benign disease. When small dogs do have malignant disease, they are, however, less likely to have haemangiosarcoma. This information is important to consider in early discussions with owners of dogs of various breed sizes., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Major challenges in clinical trials of ultra-orphan oncology diseases include limited patient availability and paucity of reliable prior data for estimating the treatment effect and, therefore, determining optimal sample size. Angiosarcoma (AS), a particularly aggressive form of soft tissue sarcoma with an incidence of about 2000 cases per year in the United States and Europe is poorly addressed by current systemic therapies. Pazopanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) is approved for the treatment of AS, with modest benefit. TRC105 (carotuximab) is a monoclonal antibody to endoglin, an essential angiogenic target highly expressed on proliferating endothelium and both tumor vessels and tumor cells in AS, that has the potential to complement VEGFR tyrosine kinase inhibitors. In a phase I/II study of soft tissue sarcoma, TRC105 combined safely with pazopanib and the combination demonstrated durable complete responses and encouraging progression-free survival (PFS). In addition, there was a suggestion of superior benefit in patients with cutaneous lesions versus those with the non-cutaneous lesions., Patients and Methods: This article describes the design of a recently initiated phase III trial of TRC105 And Pazopanib versus Pazopanib alone in patients with advanced AngioSarcoma (TAPPAS trial). Given the ultra-orphan status of the disease and the paucity of reliable prior data on PFS or overall survival (end points required for regulatory approval as a pivotal trial), an adaptive design incorporating population enrichment and sample size re-estimation was implemented. The design incorporated regulatory input from the Food and Drug Administration (FDA) and European Medicines Agency and proceeded following special protocol assessment designation by the FDA., Conclusions: It is shown that the benefit of the adaptive design as compared with a conventional single-look design arises from the learning and subsequent improvements in power that occur after an unblinded analysis of interim data., Registered on Clinicaltrials.gov: NCT02979899.

Background: There are limited treatment options for advanced non-melanoma skin cancers (NMSCs). To overcome this issue, we need to conduct clinical studies, however, there is a lack of information on how many patients with advanced NMSCs are treated annually in Japan., Objective: To investigate the actual number of advanced NMSC patients in Japan., Methods: A questionnaire survey was sent to 668 institutes to educe information on: 1) the numbers of patients with squamous cell carcinoma (SCC), extramammary Paget disease (EMPD), other skin origin carcinomas, and cutaneous angiosarcoma (CAS) admitted in 2016 and 2017; 2) the preferred first- and second-line chemotherapies; and 3) the anticipated for future development., Results: Questionnaires were returned from 383 (57.3%) institutes. They reported a total of 1765 patients over the 2 years. The annual number patients with SCC, EMPD, other skin carcinomas, and CAS was 323.5, 192.5, 126, and 240.5, respectively. We estimated the annual number of patients for all 668 institutes to be 1255.6. Current first- and second-line treatment for NMSCs were chemotherapy regimens, but immune checkpoint inhibitors were the most anticipated new drugs for SCC and CAS, while chemotherapy was still the most anticipated treatment for EMPD., Conclusion: Considering that during 2017, the number of deaths in Japan due to NMSC was reported to be 948, our estimated annual number of patients with NMSCs, 1255.6 seems to be an accurate estimation. As most of the treatment options for advanced NMSCs are outdated, the results of this study should be used to propose clinical studies., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Radiation-associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population-based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953-2014 who were later diagnosed with a secondary sarcoma in 1953-2014. Registry data, patient files, and sarcoma specimens were  analyzed to confirm diagnosis and location of RAS at or close to the RT target volume. A total of 132 512 patients were diagnosed with invasive BC during the study period. A subsequent sarcoma was diagnosed in 355 patients. After exclusion, 96 RAS were identified. Angiosarcoma (AS) was the most prevalent histology in 50 (52%) of 96 patients. However, the first radiation-associated AS was diagnosed in a patient treated for BC with breast-conserving surgery in 1984, and thereafter, the proportion of AS continuously increased. The 5-year sarcoma-specific survival was 75.1% for RAS treated with a curative intent. The distribution of histologic subtypes of RAS has changed during the 60 years of this registry study. The first radiation-associated AS was diagnosed in 1989, and presently, AS is the most common histologic subtype of RAS. It is possible that changes in BC treatment strategies are influencing the characteristics of RAS., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Radiogenic angiosarcoma of the breast (RASB) is a rare late sequela of local irradiation of the breast or chest wall after breast cancer. The prognosis of women with RASB is poor and there is no standardized therapy for this type of malignancy., Case Presentation: We present the case of a 54 year old woman with RASB (poorly differentiated angiosarcoma of the left breast; pT1, pNX, M0, L0, V0) and a history of invasive-ductal cancer of the left breast (pT1b, G2, pN0, ER positive, PR positive, HER-2/neu negative) treated in July 2012 with breast-conserving surgery, adjuvant chemotherapy with 6 cycles of epirubicin and cyclophosphamide, adjuvant irradiation of the left breast with 50 Gray, and adjuvant endocrine therapy with an aromatase inhibitor. In August 2016, a bilateral salpingo-oophorectomy was performed to remove a tumor of the left ovary, which was diagnosed as breast cancer recurrence. At the same time, a small, purple skin lesion of 1.2 cm in diameter was noted in the inner upper quadrant of the right breast. RASB was diagnosed by punch biopsy and the tumor was excised with clear margins. Imaging studies showed no evidence of further metastases. A systemic chemotherapy with 6 cycles of liposomal doxorubicin was initiated. Five months later, a local recurrence of RASB was diagnosed and mastectomy was performed. Six months later, the patient is alive with no evidence of disease. Three hundred seven cases of RASB were identified. The pooled incidence rate of RASB was 1/3754 women. The most common treatment of RASB was mastectomy in 83% of cases. Adjuvant radiotherapy or chemotherapy were rarely used with 6 and 4%, respectively, whereas in case of recurrence, chemotherapy was the mainstay of treatment, used in 58% of cases. Radiotherapy and repeated surgery were also common with 30 and 33% of cases, respectively. Overall, the prognosis of women with RASB was poor and the recurrence-free survival was short with a mean of 15.9 months. Mean overall survival was 27.4 months., Conclusion: RASB is a rare late complication of breast irradiation. The prognosis of women with RASB is poor. Surgery is the mainstay of treatment for localized disease while systemic chemotherapy and re-irradiation are appropriate for women with disseminated or recurrent RASB.

Background: The available literature on the incidence, management and prognosis of primary malignant cardiac tumors [PMCTs] is limited to single-center studies, prone to small sample size and referral bias. We used data from the Surveillance, Epidemiology, and End Results [SEER]-18 registry (between 2000 and 2014) to investigate the distribution, incidence trends and the survival rates of PMCTs., Methods: We used SEER*Stat (version 8.3.4) and the National Cancer Institute's Joinpoint Regression software (version 4.5.0.1) to calculate the incidence rates and annual percentage changes [APC] of PMCTs, respectively. We later used SPSS software (version 23) to perform Kaplan-Meier survival tests and covariate-adjusted Cox models., Results: We identified 497 patients with PMCTs, including angiosarcomas (27.3%) and Non-Hodgkin's lymphomas [NHL] (26.9%). Unlike the incidence rate of NHL (0.108 per 10 6 person-years) that increased significantly (APC=3.56%, 95% CI, [1.445 to 5.725], P=.003) over the study period, we detected no significant change (APC=1.73%, 95% CI [-3.354 to 7.081], P=.483) in the incidence of cardiac angiosarcomas (0.107 per 10 6 person-years). Moreover, our analysis showed that the overall survival of NHL is significantly better than angiosarcomas (P<.001). In addition, surgical treatment was associated with a significant improvement (P=.027) in the overall survival of PMCTs., Conclusion: Our analysis showed a significant increase in the incidence of cardiac-NHL over the past 14 years with a significantly better survival than angiosarcomas. To further characterize these rare tumors, future studies should report data on the medical history and diagnostic and treatment modalities in these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Angiosarcoma with pulmonary metastasis is a rare, fatal disease that often presents with multiple pulmonary nodules and diffuse alveolar hemorrhage. We herein review the detailed clinical characteristics of pulmonary metastatic angiosarcoma and determine a reasonable diagnostic strategy.The medical records of 11 patients with pulmonary angiosarcoma were reviewed.The mean age of the patients was 45.7 years (range, 30-71 years). All patients were male. The most common symptom was hemoptysis (8/11). Common initial misdiagnoses were tuberculosis (5/11), vasculitis (2/11), nontuberculous infectious disease (1/11), and constrictive pericarditis (1/11). Chest computed tomography (CT) of patients with hemoptysis showed bilateral, randomly distributed, variably shaped, and differently sized nodules, as well as ground-glass opacities (GGO) (8/11). The right heart was the most common primary tumor site (8/11), but the sensitivity of echocardiography was limited; CT angiography and cardiac magnetic resonance imaging (MRI) revealed more atrial masses. CT-guided needle biopsy was difficult to perform in most patients because of the small size of the nodules. The diagnosis was made by surgical biopsy of either the lung (3/9) or heart (6/9). The median overall survival of patients who underwent lung biopsy and those who underwent cardiac/pericardiac biopsy was 4.1 and 1.4 months, respectively (P = .098). The median overall survival of the 9 available patients was 5.0 months (95% confidence interval, 0.500-8.544).Angiosarcoma with pulmonary metastases should be considered in patients with hemoptysis and concurrent GGO and nodules on their chest CT scan. Careful cardiologic monitoring is necessary for these patients, even without any cardiac symptoms or signs, and enhanced cardiac MRI is the first recommendation. Surgical biopsy is reliable for histological diagnosis, but the safety of the lung biopsy should be carefully assessed. When primary cardiac tumors are identified, heart biopsy should be preferentially considered.

Background: Angiosarcoma of the scalp and face is an aggressive tumor with a high rate of local recurrence. Although many previous studies have demonstrated risk factors for poor prognosis, debate remains. We identified the predisposing factors for poor prognosis through comprehensive review of selected studies with meta-analysis., Methods: A systematic literature review and meta-analysis were performed using MEDLINE, EMBASE, and Cochrane databases. Nine variables were extracted from the included studies and evaluated based on a 5-year survival rate. The Newcastle-Ottawa scale was used to assess the quality of the studies., Results: The search strategy identified 89 publications. After screening, 11 articles were selected for review. Age, size, site of tumor, margin status, and surgery associated with poor angiosarcoma prognosis were identified., Conclusion: Although further investigation of long-term and prospective studies is needed, we identified 5 variables as predisposing factors for poor prognosis of angiosarcoma through meta-analysis. © 2016 Wiley Periodicals, Inc. Head Neck 39: 380-386, 2017., (© 2016 Wiley Periodicals, Inc.)

Purpose: To identify retrospectively prognostic factors of primary breast sarcoma and review its treatment modalities., Materials and Methods: This is a descriptive study on 30 cases of primary breast sarcoma. We carried out a univariate and multivariate analysis correlating clinical, pathological and therapeutic parameters with disease-free survival and overall survival., Results: The mean age was 46.8 years. The mean tumour size was 10cm. The 30 cases were 18 phyllodes sarcomas, eight angiosarcomas, three liposarcomas and a case of granulocytic sarcoma. Sixteen patients had adjuvant radiotherapy and only seven patients received adjuvant chemotherapy. The median follow-up was 64 months. Overall survival rates at 3 and 5 years were 49.1% and 33.7%. Disease-free survival rates at 3 and 5 years were 22.8% and 15.2% respectively. The analytical study of the following parameters: tumour size and presence or absence of node or distant metastases, showed no correlation with overall survival nor with disease-free survival. Furthermore, adjuvant radiotherapy did not improve overall survival (P=0.298; hazard ratio [HR]=1 [0.982-1.04]) nor disease-free survival (P=0.61; HR=0.942 [0.862-1.029]). By univariate analyses, we identified a correlation between overall survival, surgical margins (>1cm) (P=0005; HR=3.4 [1.217-9.919]) and tumour necrosis (P=0.028; HR=0.099 [0.014-0.682]). We did not find any independent prognostic factor by multivariate analysis., Conclusion: The prognosis of primary breast sarcoma seems to depend essentially on optimal surgical excision (margin over 1cm). The only potential histological parameter correlated with the prognosis is the presence of tumour necrosis. The histological subtype should not be considered as a prognostic marker for overall or disease-free survival in patients with primary breast sarcoma., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Midline capillary formation nuchae (MCFN) consists of blanchable pink macules located around the midline of the occiput and nape. It has been implicated in the literature as a risk factor for angiosarcoma and might be related to a decrease in innervation of the involved capillaries. Although there is ample literature on its prevalence from birth through adult life, the literature in late life is sparse. The objective of this study was to determine the prevalence in late life, whether it is truly a risk factor for angiosarcoma and whether it might be an indication of a systemic neuroendocrine effect or a local reaction. In routine skin screening examinations of 411 patients, the prevalence of MCFN increased with age ( P <.0001), by quartiles of age overall ( P =.0001), and among men only ( P =.0013). No difference in prevalence was observed across quartiles of age among women only ( P =.0688). No association was found with routine parameters that might be influenced by the systemic neuroendocrine system. Prevalence increases in old age, is not a risk factor for angiosarcoma, and might represent a response of local capillaries to normal changes in the neuroendocrine system that occur with age.

Background: Angiosarcomas are aggressive soft tissue sarcomas. Due to their rarity there is a paucity of data regarding the clinical outcome of patients with non-visceral angiosarcomas of the soft tissues. In particular, the prognostic significance of surgical margins remains controversial., Patients and Methods: We retrospectively assessed the outcome of 43 patients with localised disease suitable for surgical treatment with curative intent. The median follow-up was 7.5 years., Results: The 5-year overall survival (OS) rate was 46.2%. Sixteen patients (37.2%) were diagnosed with secondary, radiation-induced angiosarcomas. Twenty-four patients (55.8%) developed local recurrences and 15 patients (34.9%) distant metastases. Negative surgical margin emerged as the only statistically significant prognostic factor (5-year OS: R0 51.8% vs. R1/R2 17.1%, p=0.036). As indicated in the regression analysis, close and wide negative margins within the R0 subgroup led to similar outcomes., Conclusion: Angiosarcomas have a high risk of local recurrence and metastasis. Surgical resection with negative margins improves the outcome., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Medical records of 396 dogs undergoing splenectomy for treatment of a splenic mass or nodular disease were reviewed retrospectively. Overall distribution of histopathologic diagnosis and clinicopathologic features were evaluated for 325 dogs that met inclusion criteria. Dogs were dichotomized into two groups based on weight, with the statistically derived cutoff identified as 27.8 kg. Malignancy was diagnosed in 58% of dogs, with no difference between small (55%) and large (61%) dogs (P = .291). Overall, 32% of splenic masses were hemangiosarcoma (HSA), which comprised 25 and 39% of all masses in small and large dogs, respectively. The diagnosis of HSA, non-HSA malignancy, or benign splenic disease was significantly different between the groups (P = .019). Of malignant diagnoses, HSA comprised 46 and 65% of small and large dog splenic neoplasms, respectively (P = .009). In both groups, dogs with HSA were significantly more likely to have preoperative anemia, hemoabdomen, thrombocytopenia, and a blood transfusion, as compared to dogs with non-HSA malignancy or benign lesions. Overall, dogs had similar odds of having a malignant splenic lesion regardless of weight, but dogs ≤27.8 kg were significantly less likely to be diagnosed with HSA.

Angiosarcoma of the breast represents 1% of all soft tissue breast tumors. With breast-conserving therapy (BCT) as standard in the last three decades, a new type of angiosarcoma has been reported: post-irradiation angiosarcoma (PIAS). A recent study based on the SEER database found an absolute risk for PIAS of seven per 100,000 person-years for BCT patients. We present a retrospective analysis of the clinical characteristics, treatment, and outcome of six cases of PIAS treated in our institution from 1995 to 2010. Mean age at diagnosis of breast cancer was 68 years (range 54-76 years). All patients underwent BCT. Adjuvant radiotherapy was given to all patients at doses of 45-50 Gy. Mean time from adjuvant radiotherapy to PIAS was 9.2 years (range 5.3-13.8 years); median follow-up from diagnosis of PIAS was 41.8 months (range 11-102 months). At diagnosis of PIAS, mean age of patients was 78 years (range 63-87 years). All patients underwent simple mastectomy, following which one patient received chemotherapy with doxorubicin and three patients received radiation therapy. Two patients developed local recurrence, one concurrent with metastatic disease. Another patient was diagnosed after 24 months with extensive small cell lung cancer and died of disease without recurrence of PIAS. Four patients are alive without evidence of recurrence. PIAS is a very rare sarcoma occurring after BCT. Careful observation after adjuvant radiotherapy is required. Standard treatment is the surgery with simple mastectomy and adjuvant radiotherapy; chemotherapy may be considered for more advanced cases.

Due to the increased vascularity as well as the unique anatomical structure, vascular lesions, which occur in the female reproductive system are common observed and diverse by their morphology. The majority of them are benign, including vascular malformations, lesions due to vascular hyperplasia, tumors with significant vascular component and others. Malignant vascular tumors are rare in the area of the vulva accounting about 1% of all vulvar lesions with vascular origin. Kaposi sarcoma, epithelioid hemangioepithelioma and epithelioid angiosarcoma have been reported with vulvar localization. With a view to their rare incidence, nonspecific clinical manifestation and aggressive behavior associated with high mortality, we present the most common malignant tumors of vascular origin arising in the vulva, as we emphasize on their epidemiology and clinical features, differential diagnosis and therapeutic algorithms for this rare type of malignancies.

Objective: We report the results of our angiosarcoma of the liver (ASL) registry to assess the occurrence, the impact of exposures to vinyl chloride, and to quantify latency., Methods: We examined more than 73,000 death certificates of North American workers employed between 1940 and 2008., Results: We found 13 deaths of ASL among workers with vinyl chloride exposure. All 13 occurred at single plant among workers with high vinyl chloride exposure. The mean latency after first exposure was 36.5 years ranging from 24 to 56 years. No ASL deaths occurred among workers with vinyl chloride exposures after 1974, when exposures were reduced., Conclusions: We may have seen the last case of ASL among workers exposed to vinyl chloride. Nevertheless, given the long latency of this cancer, continued surveillance seems prudent.

Objective: An increase in the incidence of prostate angiosarcoma may be expected owing to the exponential increase in the use of radiotherapy for prostate carcinoma in recent decades and the possible aetiology of radiation exposure on the development of angiosarcoma in general. The objective of this study was to give an overview of cases in the literature based on a case report of prostate angiosarcoma in a hospital in the Netherlands, and to discuss optimal treatment., Material and Methods: All (related) articles In PubMed/Medline and Embase with possible cases of angiosarcoma were screened on title and abstract. A case of prostate angiosarcoma identified in the authors' institution was included., Results: The literature search yielded 13 cases of prostate angiosarcoma. The earliest six publications lack essential data. Four patients had a history of radiotherapy. The present patient developed angiosarcoma following brachytherapy for prostate cancer. Therapy consisted of radical surgery with or without chemotherapy in five cases. In eight cases curative therapy was not reported or not possible. Mean follow-up was only 1 year. Four patients died within 1 year of diagnosis, irrespective of treatment choice. One patient, treated with a combination of radical surgery and adjuvant chemotherapy, was still alive 36 months after therapy., Conclusions: The findings confirm that prostate angiosarcoma is mostly radiation induced. This patient is the first case of prostate angiosarcoma after primary brachytherapy. Angiosarcoma may occur more often in the future owing to widespread use of brachytherapy and radiotherapy of the prostate. Current guidelines on management of angiosarcoma suggest radical surgery in local disease as the primary treatment of choice.

In the study presented here, we aimed to describe the epidemiological, clinical and pathological findings of 51 canine cases with histologically-verified diagnoses of primary cardiac hemangiosarcoma (HSA). The medical data for each dog, including signalment, presenting complaints, physical examination findings, results of various diagnostic testing performed and method of treatment, were checked. In addition, all 51 cases were re-examined pathologically. The tumor occurred most frequently in older Golden Retrievers, followed by Maltese dogs and Miniature Dachshunds. Mass lesions of HSA were found more commonly in the right auricle (RAu) (25/51) and right atrium (RA) (21/51), and the RA masses were significantly (P<0.001) larger than the RAu masses. The echocardiographic detection rate of masses in the RAu group (60%; 15/25) was significantly lower than that in the RA group (95%; 20/21). Survival time was significantly (P<0.05) longer for 5 dogs that received adjuvant chemotherapy after tumor resection than for 12 dogs that did not. In this series, the Maltese (9/51) and Miniature Dachshund (7/51), as well as the Golden Retriever, were represented more frequently than other breeds. The lower echocardiographic detection rate of RAu masses compared with RA masses may be related to tumor size and/or location. The significantly longer survival time for dogs receiving adjuvant chemotherapy indicates that postoperative chemotherapy could be useful for dogs with cardiac HSA.