Incidence and Presenting Characteristics of Angiosarcoma in the US, 2001-2020.

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.

New risk factors and molecular landscapes of hepatic angiosarcoma in the Taiwanese population†.

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.

Clinical characteristics of sarcoma patients: a population-based data analysis from a German clinical cancer registry.

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.

Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

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.

Angiosarcoma in the breast: a population-based cohort from Sweden.

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.

Descriptive analysis of haemangiosarcoma occurrence in dogs enrolled in the Golden Retriever lifetime study.

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.

Association between hepatic angiosarcoma and end-stage renal disease: nationwide population-based evidence and enriched mutational signature of aristolochic acid exposure.

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.

Treatment-related thoracic soft tissue sarcomas in US breast cancer survivors: a retrospective cohort study.

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<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.

Sex differences in primary malignant cardiac tumors: A multi-institutional cohort study from National Cancer Database.

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.

Characteristics and survival outcomes of primary splenic cancers: A SEER population-based study.

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.

Development and validation of a prognostic nomogram model in primary cutaneous and subcutaneous soft tissue angiosarcoma.

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.

Stewart-Treves syndrome and other cutaneous malignancies in the context of chronic lymphedema: a systematic review.

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.

Cancer registry study of malignant hepatic vascular tumors: hepatic angiosarcomas and hepatic epithelioid hemangioendotheliomas.

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.

Plasma Metabolomics Analysis of Polyvinyl Chloride Workers Identifies Altered Processes and Candidate Biomarkers for Hepatic Hemangiosarcoma and Its Development.

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.

Breast Angiosarcoma Surveillance Study: UK national audit of management and outcomes of angiosarcoma of the breast and chest wall.

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.

Characteristics and Long-Term Risk of Breast Angiosarcoma.

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.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years.

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.

A Clinical Model of Bone Angiosarcoma Patients: A Population-based Analysis of Epidemiology, Prognosis, and Treatment.

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.

Canine cutaneous neoplasms in the metropolitan region of Goiânia, Goiás state, Brazil / Neoplasias cutâneas caninas na região metropolitana de Goiânia, Goiás, Brasil

ABSTRACT: The present study aimed to describe the occurrence and epidemiological features of skin neoplasms diagnosed in dogs in the metropolitan region of Goiânia, Goiás state, Brazil. Diagnoses from dog biopsies from 2011 to 2016 provided by a private veterinary pathology laboratory were analyzed. The main diagnoses were mast cell tumor, hemangiosarcoma, squamous cell carcinoma, malignant melanoma, and hemangioma. Highest frequency of neoplasms was found in female dogs, dogs aged > 8 years, and purebred dogs, particularly the American Pit Bull Terriers and the Poodles. Most common sites affected by the neoplasms were the limb and the head. Using multiple correspondence analysis, groups of neoplasms were found to be associated with different epidemiological features and the size of the neoplasms was associated with the biological behavior. The results of this study described predispositions and verified the importance of different types of skin neoplasms in dogs in the region being studied.(AU)

O objetivo deste estudo foi determinar a prevalência e as características epidemiológicas das neoplasias cutâneas em cães na região metropolitana de Goiânia, Goiás. Foram analisados os diagnósticos de um laboratório do setor privado de 2011 a 2016. Mastocitoma, hemangiossarcoma, carcinoma de células escamosas, melanoma maligno e hemangioma representaram os principais diagnósticos. A maioria dos casos ocorreram em cães de raças definidas, fêmeas e com idade >8 anos. American Pit Bull Terrier e Poodle foram as raças mais encontradas. As neoplasias acometeram principalmente regiões de membros e cabeça. Pela análise de correspondência múltipla, associou-se os grupos de neoplasias com diferentes características epidemiológicas e o tamanho da neoplasia com o comportamento biológico. A comparação dos resultados com pesquisas prévias possibilitou confirmar predisposições previamente descritas e verificar a importância dos diferentes tipos de neoplasias cutâneas em cães na região estudada.(AU)