• AI-assisted diagnosis
• Angiosarcoma
• Artificial intelligence
• Digital pathology
• Immunotherapy
• PD-L1 expression

• chemotherapy-free
• geriatric patient
• immunotherapy
• photodynamic therapy
• recurrent
• scalp and facial angiosarcomas
• target therapy

• Aged
• Humans
• Male
• Combined Modality Therapy
• Facial Neoplasms/therapy
• Facial Neoplasms/pathology
• Head and Neck Neoplasms/therapy
• Hemangiosarcoma/therapy
• Hemangiosarcoma/pathology
• Hemangiosarcoma/diagnosis
• Hemangiosarcoma/drug therapy
• Immunotherapy/methods
• Neoplasm Recurrence, Local/therapy
• Photochemotherapy/methods
• Scalp/pathology
• Skin Neoplasms/therapy
• Skin Neoplasms/pathology
• Treatment Outcome

• angiosarcoma
• genomics
• rare cancer
• sarcoma

• Hemangiosarcoma/genetics
• Hemangiosarcoma/pathology
• Humans
• Animals
• Genomics
• Disease Models, Animal
• Mutation

• Department of Biological Sciences Ross Lynn Fellowship
• Ralph W. and Grace M. Showalter Research Trust Fund
• Purdue University Graduate School Ross Fellowship
• P30 CA023168 NCI NIH HHS
• Walther Cancer Foundation
• HT94252410861 Congressionally Directed Medical Research Programs
• Jim and Diann Robbers Cancer Research Grant
• P30 CA023168 NCI NIH HHS
• Ralph W. and Grace M. Showalter Research Trust Fund
• Congressionally Directed Medical Research Programs
• Walther Cancer Foundation

• Epithelioid morphology
• Necrosis
• Ovarian angiosarcoma
• Survival analysis

• Humans
• Hemangiosarcoma/pathology
• Hemangiosarcoma/mortality
• Hemangiosarcoma/therapy
• Female
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/mortality
• Adult
• Survival Analysis
• Middle Aged
• Immunohistochemistry/methods

• Humans
• Skin Neoplasms/pathology
• Skin Neoplasms/diagnosis
• Diagnosis, Differential

• Humans
• Antibodies, Monoclonal, Humanized/therapeutic use
• Microsatellite Instability
• Sarcoma/diagnosis
• Sarcoma/drug therapy
• Sarcoma/genetics

• breast swelling
• breast trauma
• primary breast angiosarcoma

• Humans
• Female
• Hemangiosarcoma/diagnosis
• Hemangiosarcoma/pathology
• Hemangiosarcoma/therapy
• Breast Neoplasms/pathology
• Breast Neoplasms/therapy
• Breast Neoplasms/diagnosis
• Young Adult
• Neoplasm Recurrence, Local
• Fatal Outcome

• Anthracycline
• Neoadjuvant chemotherapy
• Soft tissue sarcomas
• Tumour immune microenvironment

• Adult
• Aged
• Female
• Humans
• Male
• Middle Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Biomarkers, Tumor
• Immunohistochemistry
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• Neoadjuvant Therapy
• Prognosis
• Sarcoma/drug therapy
• Sarcoma/mortality
• Sarcoma/immunology
• Sarcoma/pathology
• Treatment Outcome
• Tumor Microenvironment/immunology

• imaging
• immunohistochemistry
• inferior vena cava
• intimal sarcomas
• tislelizumab

• Humans
• Female
• Middle Aged
• Vena Cava, Inferior/pathology
• Sarcoma/drug therapy
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antibodies, Monoclonal, Humanized/administration & dosage
• Vascular Neoplasms/drug therapy
• Vascular Neoplasms/pathology
• Vascular Neoplasms/diagnosis
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Gemcitabine
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/therapeutic use
• Deoxycytidine/administration & dosage
• Lung Neoplasms/drug therapy
• Lung Neoplasms/secondary
• Lung Neoplasms/pathology

• Humans
• Hemangiosarcoma/diagnosis
• Hemangiosarcoma/drug therapy
• Indoles/therapeutic use
• Quinolines/therapeutic use
• Heart Neoplasms/diagnosis
• Heart Neoplasms/drug therapy

• No.82070425 National Natural Science Foundation of China
• No. 2042021kf0159 Fundamental Research Funds for the Central Universities

• Humans
• Female
• Pericardium/pathology
• Hemangiosarcoma/pathology
• Hemangiosarcoma/diagnosis
• Hemangiosarcoma/therapy
• Adult
• Prognosis
• Heart Neoplasms/diagnosis
• Heart Neoplasms/pathology
• Heart Neoplasms/therapy
• Pericardial Effusion/pathology
• Pericardial Effusion/diagnosis

• Angiosarcoma
• cutaneous angiosarcoma
• masquerade syndrome
• periorbital edema

• Male
• Humans
• Aged
• Hemangiosarcoma/diagnosis
• Hemangiosarcoma/therapy
• Hemangiosarcoma/pathology
• Endothelial Cells/pathology
• Skin Neoplasms/diagnosis
• Skin Neoplasms/therapy
• Edema/diagnosis
• Edema/etiology

• angiosarcoma
• cancer
• checkpoint
• immunotherapy
• sarcoma
• soft tissue

• Humans
• Nivolumab/therapeutic use
• Ipilimumab/therapeutic use
• Hemangiosarcoma/drug therapy
• Antineoplastic Agents, Immunological/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols

• head and neck cancer
• malignant disease and immunosuppression
• prevention
• screening (oncology)
• skin cancer

• Adult
• Infant
• Humans
• Male
• Kasabach-Merritt Syndrome/diagnosis
• Kasabach-Merritt Syndrome/complications
• Hemangiosarcoma/complications
• Hemangiosarcoma/diagnosis
• Hemangiosarcoma/pathology
• Neoplasm Recurrence, Local/complications
• Hemangioendothelioma/complications
• Hemangioendothelioma/diagnosis
• Disseminated Intravascular Coagulation/complications

• Case report
• Diagnosis
• Ovarian
• Primary angiosarcoma
• Prognosis
• Therapy

• Angiosarcoma
• Immunoscore
• Molecular biology
• RNA-seq

• Humans
• B7-H1 Antigen
• Hemangiosarcoma/genetics
• Prognosis
• Skin Neoplasms/genetics
• Skin Neoplasms/pathology
• Tumor Microenvironment

• Conselleria Sanidad, Comunidad Valenciana

• adoptive T-cell therapies
• immune checkpoint blockade
• immunotherapy
• soft tissue sarcomas

• hepatic angiosarcoma
• ipilimumab
• nivolumab
• splenic angiosarcoma

• Case report
• Ipilimumab
• Nivolumab
• Primary pleural angiosarcoma

• anlotinib
• camrelizumab
• hepatic angiosarcoma
• immunotargeted therapy
• interventional treatment (TACE)

• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Sarcoma/drug therapy
• Liposarcoma
• Immunotherapy/methods

• angiosarcoma
• biomarker
• genetics
• immunotherapy
• sarcoma
• tumor microenvironment

• metastatic angiosarcoma

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

• Apoptosis Regulatory Proteins
• B7-H1 Antigen/metabolism
• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Immunotherapy
• Neoplasms/drug therapy
• Neoplasms/metabolism

• angiosarcoma
• mage-a4, ny-eso
• pd-1
• pd-l1

• Aged
• B7-H1 Antigen
• Biomarkers, Tumor/metabolism
• Esophageal Neoplasms/pathology
• Esophageal Squamous Cell Carcinoma
• Hemangiosarcoma/therapy
• Humans
• Ligands
• Male
• Melanoma/genetics
• Pain
• Prognosis
• Programmed Cell Death 1 Receptor
• Skin Neoplasms/metabolism

• Adoptive cellular therapy
• Immune checkpoint inhibitors
• Immunotherapy
• Soft tissue sarcoma
• Tertiary lymphoid structure
• Tumor microenvironment

• Adult
• Biomarkers, Tumor
• Humans
• Immunotherapy
• Liposarcoma/pathology
• Male
• Sarcoma/pathology
• Soft Tissue Neoplasms

• P30 CA008748 NCI NIH HHS

• angiosarcoma
• case report
• epithelioid
• ground glass opacity
• lung cancer
• pulmonary nodule
• thyroid carcinoma

We present a case of a 32-year-old female presenting with shortness of breath and increasing oxygen requirements. Further imaging discovered a large mass extending circumferentially into the pericardium, cardiac wall, and chambers, involving the anterior and middle mediastinum. Direct tissue biopsy of the mass for a diagnosis was unsafe. Therefore, advanced flow cytometric analysis for tumor marker expression of the malignant effusion was used to differentiate the mass as a vascular sarcoma, consistent with cardiac angiosarcoma. Additionally, cytometric analysis for programmed cell death protein 1 (PD1), programmed death-ligand 1 (PDL1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) was also performed; a study seldom investigated for angiosarcomas but may have advantages over immunohistochemical analysis.

• Cutaneous angiosarcoma (CAS)
• Ki-67
• Overall survival (OS)
• Programmed death ligand-1 (PD-L1)
• Tumor-infiltrating lymphocytes (TILs)
• c-MYC

• Aged
• B7-H1 Antigen/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Female
• Forkhead Transcription Factors/metabolism
• Hemangiosarcoma/metabolism
• Hemangiosarcoma/pathology
• Hemangiosarcoma/surgery
• Humans
• Ki-67 Antigen/metabolism
• Lymphocytes, Tumor-Infiltrating/metabolism
• Male
• Prognosis
• Programmed Cell Death 1 Receptor/metabolism
• Retrospective Studies
• Tumor Microenvironment

• PD1/PDL1
• adoptive cell therapy
• advanced disease
• histotypes
• immune checkpoint inhibitors
• immunotherapy
• soft tissue sarcoma
• tumour microenvironment

Angiosarcoma is a histologically and molecularly heterogeneous vascular neoplasm with aggressive clinical behavior. Emerging data suggests that immune checkpoint blockade (ICB) is efficacious against some angiosarcomas, particularly cutaneous angiosarcoma of the head and neck (CHN).

Patients with histologically confirmed angiosarcoma treated with ICB-based therapy at a comprehensive cancer center were retrospectively identified. Clinical characteristics and the results of targeted exome sequencing, transcriptome sequencing, and immunohistochemistry analyses were examined for correlation with clinical benefit. Durable clinical benefit was defined as a progression-free survival (PFS) of ≥16 weeks.

For the 35 patients included in the analyses, median PFS and median overall survival (OS) from the time of first ICB-based treatment were 11.9 (95% CI 7.4 to 31.9) and 42.5 (95% CI 19.6 to 114.2) weeks, respectively. Thirteen patients (37%) had PFS ≥16 weeks. Clinical factors associated with longer PFS and longer OS in multivariate analyses were ICB plus other therapy regimens, CHN disease, and white race. Three of 10 patients with CHN angiosarcoma evaluable for tumor mutational burden (TMB) had a TMB ≥10. Five of six patients with CHN angiosarcoma evaluable for mutational signature analysis had a dominant mutational signature associated with ultraviolet (UV) light. No individual gene or genomic pathway was significantly associated with PFS or OS; neither were TMB or UV signature status. Analyses of whole transcriptomes from nine patient tumor samples found upregulation of angiogenesis, inflammatory response, and KRAS signaling pathways, among others, in patients with PFS ≥16 weeks, as well as higher levels of cytotoxic T cells, dendritic cells, and natural killer cells. Patients with PFS <16 weeks had higher numbers of cancer-associated fibroblasts. Immunohistochemistry findings for 12 patients with baseline samples available suggest that neither PD-L1 expression nor presence of tumor-infiltrating lymphocytes at baseline appears necessary for a response to ICB-based therapy.

ICB-based therapy benefits only a subset of angiosarcoma patients. Patients with CHN angiosarcoma are more likely to have PFS ≥16 weeks, a dominant UV mutational signature, and higher TMB than angiosarcomas arising from other primary sites. However, clinical benefit was seen in other angiosarcomas also and was not restricted to tumors with a high TMB, a dominant UV signature, PD-L1 expression, or presence of tumor infiltrating lymphocytes at baseline.

• Biomarkers, Tumor
• Immunotherapy
• Sarcoma

• angiosarcoma
• clinical
• pleural angiosarcoma
• prognosis
• retrospective

• Adult
• Aged
• Aged, 80 and over
• Hemangiosarcoma/mortality
• Hemangiosarcoma/therapy
• Hemothorax
• Humans
• Middle Aged
• Pleural Effusion
• Prognosis
• Retrospective Studies
• Survival Rate
• Young Adult

Angiosarcoma (AS) is a rare malignancy with a poor prognosis. It can develop spontaneously or due to previous radiotherapy (RT), ultraviolet (UV) radiation, or lymphoedema (Stewart Treves AS). Novel therapeutic approaches are needed, but progress is hindered because of the heterogeneity and rarity of AS. In order to explore the potential of immune checkpoint inhibition (ICI), we investigated the protein expression of programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and CD8 + T cells in 165 AS cases in relation to AS subgroups based on clinical classification and in relation to whole-genome methylation profiling based clusters (A1, A2, B1, B2). High PD-L1 and PD-1 expression were predominantly shown in UV-associated, visceral, and soft tissue AS. RT-associated AS showed predominantly high PD-1 expression. CD8 + T cell infiltration was present in the majority of AS samples. Within the UV-associated AS, two different clusters can be distinguished by DNA methylation profiling. Cases in cluster A1 showed higher PD-1 (p = 0.015), PD-L1 (p = 0.015), and CD8 + T cells (p = 0.008) compared to those in cluster B2, suggesting that these UV-AS tumors are more immunogenic than B2 tumors showing a difference even within one subgroup. In soft tissue AS, combined PD-1 and PD-L1 expression showed a trend toward poor survival (p = 0.051), whereas in UV-associated AS, PD-1 expression correlated with better survival (p = 0.035). In conclusion, we show the presence of PD-1, PD-L1, and CD8 + T cells in the majority of AS but reveal differences between and within AS subgroups, providing prognostic information and indicating to be predictive for ICI.

• Angiosarcoma
• Immune checkpoint inhibition
• Programmed cell death 1
• Programmed death-ligand 1 (PD-L1)
• Subgroups

Radiation-associated angiosarcoma (RAAS) is a rare complication among patients treated with radiation therapy for breast cancer. Hyperfractionated-accelerated reirradiation (HART) improves local control after surgery. Proton therapy may further improve the therapeutic ratio by mitigating potential toxicity.

Six patients enrolled in a prospective registry with localized RAAS received HART with proton therapy between 2015 and 2021. HART was delivered twice or thrice daily in fraction sizes of 1.5 or 1.0 Gy, respectively. All patients received 45 Gy to a large elective volume followed by boosts to a median dose of 65 (range, 60-75) Gy. Toxicity was recorded prospectively by using the Common Terminology Criteria for Adverse Events, version 4.0.

The median follow-up duration was 1.5 (range, 0.25-2.9) years. The median age at RAAS diagnosis was 73 (range, 60-83) years with a median latency of 8.9 (range, 5-14) years between radiation therapy completion and RAAS diagnosis. The median mean heart dose was 2.2 (range, 0.1-4.96) Gy. HART was delivered postoperatively (n = 1), preoperatively (n = 3), preoperatively for local recurrence after initial management with mastectomy (n = 1), and as definitive treatment (n = 1). All patients had local control of disease throughout follow-up. Three of 4 patients treated preoperatively had a pathologic complete response. The patient treated definitively had a complete metabolic response on her posttreatment PET/CT (positron emission tomography–computed tomography) scan. Two patients developed distant metastatic disease despite local control and died of their disease. Acute grade 3 toxicity occurred in 3 patients: 2 patients undergoing preoperative HART experienced wound dehiscence and 1 postoperatively developed grade 3 wound infection, which resolved.

HART with proton therapy appears effective for local control of RAAS with a high rate of pathologic complete response and no local recurrences to date. However, vigilant surveillance for distant metastasis should occur. Toxicity is comparable to that in photon/electron series. Proton therapy for RAAS may maximize normal tissue sparing in this large-volume reirradiation setting.

• Angiosarcoma
• Anti-PD-1 antibody
• Mouse model

This study was designed to establish and validate promising and reliable nomograms for predicting the survival of angiosarcoma (AS) patients.

The Surveillance, Epidemiology, and End Results database was queried to collect the clinical information of 785 AS patients between 2004 and 2015. Data were split into a training cohort (n = 549) and a validation cohort (n = 236) without any preference. Univariate Cox and multivariate Cox regression analyses were performed to analyze the clinical parameters. Independent prognostic factors were then identified. Two nomograms were constructed to predict overall survival (OS) and cancer‐specific survival (CSS) at 3 and 5 years. Finally, the models were evaluated using concordance indices (C‐indices), calibration plots, and decision curve analysis (DCA).

Based on the inclusion and exclusion criteria, 785 individuals were included in this analysis. Univariate and multivariate Cox regression analyses revealed that age, tumor size, and stage were prognostic factors independently associated with the OS of AS. Tumor site, tumor size, and stage were associated with the CSS of AS. Based on the statistical results and clinical significance of variables, nomograms were built. The nomograms for OS and CSS had C‐indices of 0.666 and 0.654, respectively. The calibration curves showed good agreement between the predictive values and the actual values. DCA also indicated that the nomograms were clinically useful.

We established nomograms with good predictive ability that could provide clinicians with better predictions about the clinical outcomes of AS patients.

• SEER
• angiosarcoma
• nomogram
• prognosis

• anti-pd-1
• case report
• immunotherapy
• pembrolizumab
• pleural epithelioid angiosarcoma

• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Male
• Middle Aged
• Pleura/pathology
• Pleural Neoplasms/diagnostic imaging
• Pleural Neoplasms/drug therapy
• Pleural Neoplasms/pathology
• Sarcoma/diagnostic imaging
• Sarcoma/drug therapy
• Sarcoma/pathology
• Tomography, X-Ray Computed

Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study.

This is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used.

Overall, there were 16 evaluable patients. Median age was 68 years (range, 25–81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3–4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR.

The combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.

NCT02834013.

• Clinical Trials
• Combination
• Drug Therapy
• Immunotherapy
• Phase II as Topic
• Sarcoma