RARE DISEASE
Angiosarcoma
Angiosarcoma
Angiosarcoma
Drug discovery
3
drugs
With orphan designations
Overview
Angiosarcoma is a rare, aggressive endothelial malignancy comprising 1–2% of soft tissue sarcomas. It commonly arises in cutaneous sites (60% of cases), particularly the head/neck, with visceral or breast involvement linked to prior radiation, chronic lymphedema, or environmental carcinogens [1][2][16]. Diagnosis relies on histopathology and immunohistochemistry (CD31, ERG positivity), supported by imaging (CT/MRI) for staging. Treatment combines surgery, adjuvant radiotherapy (>70 Gy for unresectable cases), and taxane/anthracycline-based chemotherapy, with emerging roles for immunotherapy and targeted therapies in advanced disease [1][3][13].
Population
Median age at diagnosis: 71 years, with 54.5% female predominance overall [2][11].
Secondary angiosarcomas disproportionately affect women (breast/chest wall) and men (head/neck), often linked to prior radiotherapy [2][16].
Incidence rising to >1,000 annual US cases, driven by increased secondary cases [2][11].
Therapies
First-line: Wide-margin resection ± adjuvant radiotherapy (local control: 43% 5-year DFS with combined therapy) [1][18].
Systemic therapy: Weekly paclitaxel (median OS: 18.6 months) or liposomal doxorubicin; taxanes preferred for cutaneous subtypes [1][3][13].
Emerging options: Anti-PD-1 immunotherapy (e.g., pembrolizumab) and VEGF inhibitors (pazopanib) in trials, particularly for metastatic disease [3][8][15].
Categories: rare circulatory system diseases, rare developmental anomalies during embryogenesis, rare neoplastic diseases
Research Papers
1,290 drug discovery papers about Angiosarcoma, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,290 drug discovery papers about Angiosarcoma, with 1 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-08 | Primary adrenal epithelioid angiosarcoma: An extraordinarily rare malignancy with a challenging diagnosis.
Adrenal epithelioid angiosarcoma is an exceedingly rare vascular endothelial neoplasm, accounting for a minute fraction of sarcomas with fewer than 60 cases reported in the medical literature. We report the case of a 70-year-old female with primary adrenal epithelioid angiosarcoma, presenting with a rapidly enlarging right adrenal mass and associated severe right upper quadrant pain. Biochemical testing revealed that the mass was nonfunctional, and contrast-enhanced computed tomography revealed a large, heterogeneously enhancing lesion with inferior vena cava compression. Given rapid interval growth and severe symptoms, she underwent laparoscopic adrenalectomy, and histopathology with immunohistochemistry confirmed a diagnosis of primary adrenal epithelioid angiosarcoma. Postoperative management included paclitaxel chemotherapy, and the patient has remained disease-free for 2 years post-operation. This case emphasizes that the clinical and imaging features of adrenal epithelioid angiosarcoma are nonspecific, and definitive diagnosis requires surgical pathology with vascular marker staining to avoid misclassification as metastatic carcinoma. Timely resection in combination with chemotherapy can yield favorable outcomes despite this tumor's aggressive behavior and overall poor prognosis.
2026-08-08 | Multimodality imaging features of primary mammary angiosarcoma: a case report with delayed osseous metastases.
Primary angiosarcoma of the breast is an uncommon and aggressive vascular malignancy that typically affects young women and poses diagnostic and therapeutic challenges. We report the case of a 26-year-old nulliparous woman who presented with progressive left breast swelling over approximately 18 months. Clinical examination revealed diffuse tender swelling without skin discoloration, nipple changes, or palpable lymphadenopathy. Ultrasonography demonstrated a complex cystic mass with thick septations and increased vascularity, while mammography showed global asymmetry of the left breast without suspicious calcifications. Breast MRI revealed a large 8.4 cm heterogeneously enhancing mass in the upper outer quadrant with possible focal skin involvement, but no chest wall invasion or nodal disease. Initial staging with 18F-FDG PET/CT showed no distant metastases. The patient underwent left nipple-sparing mastectomy, and histopathological examination confirmed intermediate-grade primary mammary angiosarcoma, FNCLCC grade 2. Subsequent re-excision achieved clear surgical margins. She received adjuvant ifosfamide-epirubicin chemotherapy and radiotherapy. Initial follow-up imaging showed no residual or recurrent disease. However, 14 months after completion of treatment, follow-up 18F-FDG PET/CT demonstrated new FDG-avid lytic lesions in the sacral and iliac bones, and Breast MRI revealed a small enhancing sternal lesion, consistent with delayed osseous metastatic disease. The patient was treated with palliative radiotherapy and systemic therapy. This case highlights the diagnostic complexity of primary breast angiosarcoma, its potential for delayed hematogenous osseous spread, and the value of multimodality imaging in diagnosis, staging, treatment planning, and surveillance.
2026-08-04 | Selective Transarterial Embolization for Refractory Bleeding in Advanced Scalp Angiosarcoma: Two Cases.
Cutaneous angiosarcoma of the scalp is a highly aggressive vascular malignancy that predominantly affects elderly individuals and may cause severe tumor bleeding during disease progression. Hemorrhage from ulcerated tumors is often difficult to control, particularly in patients previously treated with chemoradiotherapy. We report two cases of advanced scalp angiosarcoma in which refractory tumor bleeding was successfully controlled by selective transarterial embolization. The first patient, a 75-year-old man with recurrent angiosarcoma of the frontal scalp region after multiple systemic therapies and radiotherapy, developed repeated arterial bleeding from ulcerated lesions requiring transfusion support. Angiography identified tumor-feeding branches of the superficial temporal artery and angular artery, and embolization achieved immediate hemostasis. A second embolization procedure was required for recurrent bleeding. The second patient, a 75-year-old woman, also developed persistent bleeding from a progressive scalp tumor despite chemoradiotherapy. Selective arterial embolization resulted in rapid and sustained bleeding control without major complications. These cases suggest that selective transarterial embolization may provide rapid control of refractory arterial tumor bleeding and reduce local treatment burden in selected patients with advanced scalp angiosarcoma.
2026-08-02 | When a haematoma is not a haematoma.
Cutaneous angiosarcoma (cAS) is a rare but highly aggressive vascular malignancy, often associated with chronic lymphoedema or previous radiotherapy. Its nonspecific clinical presentation can mimic benign conditions, leading to diagnostic delays. We report the case of a 70-year-old woman with chronic lymphoedema of the right arm following mastectomy and lymphadenectomy for breast cancer. She presented with a slowly enlarging haematoma-like lesion. Magnetic resonance imaging (MRI) performed externally suggested a benign haematoma. Due to progressive changes, the patient was referred to our department. High-resolution sonography revealed irregular dermal and subcutaneous vasculature with marked hyperperfusion. Deep skin biopsy demonstrated a vascular neoplasm composed of pleomorphic endothelial cells expressing ERG, CD31, D2-40 and c-Myc, with a high Ki-67 proliferation index, consistent with the diagnosis of cAS (Stewart-Treves syndrome). Computed tomography staging excluded metastatic disease, and systemic paclitaxel therapy was initiated. This case underlines the often inconspicuous clinical presentation of cAS and the limited diagnostic value of MRI for superficial lesions. High-resolution sonography may provide an important, noninvasive diagnostic clue by revealing marked hypervascularity, thereby prompting timely biopsy and improving early detection of this aggressive tumour.
2026-07-31 | Right atrial rupture due to cardiac angiosarcoma without haemodynamic collapse: a case report of successful multidisciplinary management.
Malignant tumours account for approximately 20%-30% of primary cardiac tumours, and reports remain rare. Cardiac angiosarcoma is a representative type, but prognosis is extremely poor: the median survival is about 4 months in unresectable cases and 14 months after complete resection [Patel SD, Peterson A, Bartczak A, Lee S, Chojnowski S, Gajewski P, et al. Med Sci Monit 2014;20:103-9].Approximately 29% of angiosarcomas present with metastasis at diagnosis, and the presence of pericardial effusion suggests pericardial invasion. Evidence regarding chemotherapy remains limited, and no standardized treatment has been established for metastatic primary cardiac tumours. We report a case of cardiac angiosarcoma in a 74-year-old man. At the time of presentation, masses were detected in the right atrium and the apex of the left ventricle. The right atrial tumour extended widely along the atrial wall and partially formed fistulous tracts, resulting in direct communication of blood flow from the right atrium into the pericardial cavity. Surgical tumour resection with atrial wall reconstruction was performed, and chemotherapy was initiated following histopathological confirmation. Due to their poor prognosis, cardiac tumours are often managed with palliative care. This case highlights two important points: first, cardiac angiosarcoma can cause atrial wall destruction and rupture, leading to direct communication between the atrium and pericardial space; second, even in cases of primary cardiac angiosarcoma with pulmonary metastases, appropriate cardiac surgery combined with chemotherapy may improve patient outcomes.
antibodies
2026-08-01 | Immune checkpoint inhibitor rechallenge after pazopanib treatment in primary pulmonary angiosarcoma: A case report.
Primary pulmonary angiosarcoma is a rare malignancy with limited therapeutic options. We report a case of primary pulmonary angiosarcoma in which tumor regression was achieved with immune checkpoint inhibitor (ICI) rechallenge following pazopanib therapy. The tumor showed strong PD-L1 expression and infiltration of CD3+, CD4+, and CD8+ T cells without CD20+ B cells. After disease control with atezolizumab, pazopanib induced tumor shrinkage but was followed by disease progression. Pembrolizumab rechallenge resulted in tumor regression and sustained benefit. This case suggests that sequential VEGF-targeted therapy and PD-1 blockade may contribute to renewed sensitivity to ICI in tumors with a T-cell-inflamed microenvironment.
2026-05-10 | The case for tumour-agnostic reimbursement of dual immunotherapy.
Barjesteh van Waalwijk van Doorn-Khosrovani and colleagues raise important questions about this recommendation for tumour-agnostic reimbursement of nivolumab and ipilimumab in Australia. We respectfully offer a counterpoint and endorse the broad coverage. In 2025, Pharmaceutical Benefits Advisory Committee (PBAC) proposed that prescribing nivolumab and ipilimumab be guided by clinical judgement informed by the best available evidence for undefined "immunotherapy-sensitive" advanced or metastatic cancers, and, in January 2026 made a similar recommendation for pembrolizumab. Patients with rare and ultra-rare cancers, including but not limited to angiosarcoma, alveolar soft part sarcoma, gestational trophoblastic disease, small cell carcinoma of the ovary (hypercalcemic type), and adrenocortical carcinoma, face profound unmet need. Within many of these diseases, a subset of patients derives substantial benefit from immunotherapy. For example, the SWOG DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial, the largest prospective evaluation of nivolumab plus ipilimumab in rare/ultra-rare cancers, demonstrated clinically meaningful activity across multiple histologies, without biomarker selection. Notably, some patients with metastatic disease remain disease-free years after treatment, outcomes rarely achieved with chemotherapy or supportive care in refractory settings. Therefore, concerns that biomarker-agnostic approval signals an evidentiary retreat overlook both our incomplete understanding immune sensitivity and the global access limits to comprehensive genomic testing. Importantly, clinical judgement is not arbitrary; it reflects training, experience, ethical reasoning, and patient-centred decision making. The question is whether demanding perfect evidence should prevent access to potentially transformative treatment. Grounded in evidence and expertise, PBAC's decision prioritises meaningful access to effective therapy for patients with few alternatives.
2026-05-04 | Pembrolizumab as an Off-Label Treatment of Facial Angiosarcoma: A Case Report.
of Case: We report an atypical case of cutaneous angiosarcoma presenting as unilateral nasal swelling in an elderly male. The lesion was unresponsive to topical and antibiotic therapy. Diagnosis was confirmed after surgical excision, and disease control was ultimately achieved through radiation and off-label use of pembrolizumab. Patient Info: A 79-year-old male with a history of squamous cell carcinoma presented with a 1–2 month history of erythematous, scaly swelling of the left nasal tip and ala. Family history was notable for nonmelanoma skin cancer. Initial differential diagnoses included contact dermatitis, rosacea, and rhinophyma. A shave biopsy revealed actinic damage but no malignancy. Following persistent symptoms and referral to plastic surgery, debulking surgery was performed. Histopathology confirmed cutaneous angiosarcoma. The patient declined wide local excision and instead underwent a 4-week course of hypofractionated radiation. Subsequent imaging showed regional lymph node recurrence. He declined biopsy and surgery, and was started on off-label pembrolizumab immunotherapy for disease control. Following immunotherapy, the patient experienced sustained remission with no clinical or radiographic evidence of disease four years post-treatment. Cutaneous angiosarcoma is a rare, aggressive malignancy with a poor prognosis. This case illustrates the importance of considering angiosarcoma in atypical facial lesions and demonstrates disease control using a non-traditional, patient-centered treatment strategy. Immunotherapy with pembrolizumab may offer a promising option in select patients, particularly those with contraindications to extensive surgery.
2026-03-01 | 170P AI-assisted systematic review and pooled analysis of anthracycline- versus taxane-based chemotherapy in advanced or metastatic angiosarcoma
Ridaforolimus were evaluated.PRRX1 gain and loss-of-function studies were performed in vitro and in vivo.Results: Treated tumors showed enrichment of stemness-related pathways, including epithelial-mesenchymal transition, and overexpression of SOX2, KLF4, and PRRX1, with increased Ng2+ MSC and fibroblast/chondrocyte progenitor signatures.PRRX1 knockdown reduced proliferation and increased doxorubicin sensitivity, whereas PRRX1 overexpression induced resistance in vitro and expanded the tumor-initiating cell population with a 7-fold increase in stem cell frequency by in vivo limitingdilution analysis.Treated tumors also exhibited activation of the PI3K-AKT-mTOR pathway and upregulation of IGF1 and IGF2, with elevated mTOR activity confirmed by phospho-S6 IHC.Combined IGF blockade (Xentuzumab) and mTOR inhibition (Ridaforolimus) significantly suppressed growth of chemotherapy-experienced tumors.Conclusions: CDS is driven by an undruggable fusion oncogene and rapidly develops chemoresistance.We show that chemotherapy induces IGF-PI3K-mTOR activation and a PRRX1-associated stemness program.Targeting IGF ligands and mTOR suppresses growth of chemotherapy-treated tumors, and PRRX1 acts as a key regulator of stemness and resistance.We have identified a targetable vulnerability in CDS, and further investigation of the link between IGF/mTOR signaling and PRRX1-driven stemness is required.
2026-02-16 | Postradiation angiosarcoma of the breast: a 25-year single-institution analysis of clinicopathological characteristics and immunohistochemical biomarker study.
We examined the clinicopathologic features and immunohistochemical expression of commonly tested biomarkers relevant to targeted therapy in postradiation angiosarcoma (PRAS) of the breast, aiming to better understand tumor biology and provide baseline data on tumor biomarkers to inform future therapeutic strategies for PRAS. Clinicopathologic features, outcomes, and the immunohistochemical expression of tumor biomarkers, including human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and DNA mismatch repair proteins (MMR), were analyzed in breast PRAS specimens diagnosed from 2000 to 2024. A total of 24 breast PRAS specimens from 18 patients were included in the study. All PRAS patients were female, with a median age of 72 years at the time of diagnosis. High-grade tumors were observed in 47%, 43%, and 65% of specimens according to Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC), Donnell-Rosen, and Kuba scoring methods, respectively. Surgical intervention, adjuvant chemotherapy, and radiotherapy were administered to 100%, 29%, and 23% of patients, respectively. Five patients (29%) died from the disease during a median follow-up period of 37 months. Exploratory analysis showed there was no significant association between histologic grade and overall survival, regardless of the grading system used. All PRASs were MMR-proficient with a low number of tumor-infiltrating lymphocytes (TILs) and exhibited an absence of HER2 protein expression. PD-L1 was positive in seven (32%) specimens and positively correlated with stromal TILs. Our findings suggest that breast PRAS are genomically stable and poorly immunogenic, and are likely ineligible for any HER2-targeted therapies based on current approval criteria. A subset of specimens demonstrated PD-L1 positivity, underscoring the need for further investigation of immunotherapy with anti-PD1/PD-L1 immune checkpoint inhibitors as a potential treatment option.
proteins
2026-01-29 | Hepatic Angiosarcoma Mimicking Sinusoidal Obstruction Syndrome: A Case Report.
Hepatic angiosarcoma (HAS) is an uncommon malignant tumor that is often misdiagnosed because of its nonspecific presentation and overlapping imaging findings with benign vascular tumors. Sinusoidal obstruction syndrome (SOS) is a disorder of hepatic microcirculation, usually associated with myeloablative chemotherapy and hematopoietic stem cell transplantation. The clinical and pathological overlap between SOS and hepatic angiosarcoma may complicate the diagnosis of hepatic angiosarcoma, as illustrated by this case. We report the case of a sixty-year-old man who presented to the emergency department with progressive jaundice, abdominal discomfort, and weight loss exceeding 5% of his baseline. Laboratory workup revealed a predominantly cholestatic pattern, and serologies for viral, autoimmune, and metabolic liver diseases were negative. Also, there were no known risk factors for liver disease or SOS. Repeated imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a large vascular hepatic lesion, suggestive of a benign lesion, and Doppler revealed findings compatible with SOS. Liver biopsy and hemodynamic studies indicated hepatic outflow obstruction. After clinical deterioration and expert multidisciplinary review of imaging and histology, malignant endothelial proliferation consistent with hepatic angiosarcoma was identified. Hepatic angiosarcoma can closely mimic SOS morphologically and hemodynamically. The absence of identifiable risk factors and the progressive evolution of hepatic changes should raise suspicion of malignancy, prompting multidisciplinary reassessment and careful histologic review.
2026-01-15 | Angiosarcoma developing in an ovarian fibroma: A case report.
Angiosarcomas are malignant vascular tumors primarily located in the dermis or soft tissues predominantly in the head and neck region. Ovarian localization is extremely rare, with only a few published cases. A 63-year-old patient was admitted to the hospital due to severe pain in the hypogastric and abdominal regions. The condition was interpreted as an acute abdomen and referred to surgery, and an ovarian tumor that measured 23cm×11cm×5cm and weighed 7500g was resected. Macroscopically, the cut surface showed two well-defined areas: one consisting of a matte white tissue with a fascicular appearance and firm consistency and the other hemorrhagic with necrotic areas. Histological examination revealed two patterns: one characterized by a proliferation of spindle-shaped cells without atypia, and the other by neoplastic proliferation with marked atypia, forming vascular channels or fascicles. The vascular component was positive for CD31, CD34, and ERG. The findings were interpreted as an angiosarcoma associated with a fibroma, and the patient died in the immediate postoperative period. The low incidence and ominous prognosis of primary or metastatic ovarian angiosarcomas have been confirmed. Regarding the histogenesis, a strong likelihood exists of a relationship with the ovary's rich vascular network. In both well-differentiated and poorly differentiated cases, it is crucial to consider differential diagnoses and perform immunohistochemical techniques, which can assist in achieving an accurate diagnosis. The association between fibroma and angiosarcoma is poorly understood and the histogenesis remains unclear.
2026-01-07 | Adult urologic sarcomas: a single institution experience over 25 years.
Genitourinary (GU) sarcomas are rare soft tissue malignancies, comprising around 2% of all GU cancers. Due to their rarity, limited data exist on optimal management and long-term outcomes. This study presents a 25-year single-institution experience, evaluating clinical presentation, treatment strategies, and survival outcomes, aims to identify trends over time and potential predictors of prognosis. A retrospective review was conducted of patients aged ≥18 years diagnosed with GU sarcomas at the University of Iowa Hospitals and Clinics (1998-2023). Data on tumor subtype, staging, histopathology, treatment modalities, and survival outcomes were analyzed. Kaplan-Meier analysis estimated recurrence-free survival (RFS) and overall survival (OS). Among 33 cases, the most common presentations in order of frequency were liposarcoma (LPS) (n = 15), leiomyosarcoma (LMS) (n = 12), rhabdomyosarcoma (RMS) (n = 5), and angiosarcoma (n = 1). Paratesticular tumors (n = 23) were most frequent, followed by bladder (n = 5), prostate (n = 2), and kidney (n = 2). The median age was 51 for LMS, 60 for LPS, and 24 for RMS. LMS had higher stage (66.67%), grade (83.33%), recurrence (25.00%), and mortality (41.67%) rates compared to LPS (recurrence: 13.33%, mortality: 20.00%). At 36 months, RFS was 63% (95% CI: 39%-79%), and OS was 81% (95% CI: 57%-92%) for the entire cohort. Follow-up duration was 19.9 months for LMS and 33.8 months for LPS. Surgical resection remains the mainstay of treatment for GU sarcomas. Margin status, tumor grade, and size are key prognostic factors. LMS carries the highest recurrence risk, and RMS exhibits aggressive progression. Further investigation into targeted therapies is warranted to improve outcomes.
2025-10-20 | Characteristics, Outcomes, and Risk Factors in Primary and Secondary Angiosarcoma: A Retrospective Cohort Study.
Angiosarcomas (ASs) are a heterogeneous subtype of soft tissue sarcomas. They can be subdivided into primary and secondary AS, with secondary AS being predominant, particularly those following radiotherapy. The aim of this study was first to analyze our patient cohort on a descriptive level and then to identify possible risk factors with regard to one and 5-year survival using logistic regression. The study was designed as a retrospective, single-center cohort study. All patients with histologically confirmed AS over 18 years of age were included in the study. Binary logistic regression was used for univariate analysis screening of continuous or dichotomous variables, respectively. For multivariate analysis, binary multivariate logistic regression was performed to assess independent associations between chosen variables and AS. A total of 39 patients were included in this study. 14 (35.9%) had primary and 25 (64%) had secondary AS. Women were more frequently affected (76.9%) than men (23.1%). The 1-year survival rate was 87.2%, and the 5-year survival rate was 51.3%. In the logistic regression analyses, nicotine consumption and a history of carcinoma were identified as significant factors influencing the 1-year survival rate. For the 5-year survival rate, only breast cancer was found to be a significant influencing factor in the univariate analysis. Based on univariate logistic regression, all variables with a p value of < 0.1 were chosen to be included into multivariate analysis. The multivariate analysis showed diabetes mellitus (p=0.067) with an association to influence the 5-year survival rate. We were able to show that the proportion of secondary ASs is predominant. These occur after radiation treatment of the breast. Diabetes mellitus may be associated with reduced 5-year survival, although this finding did not reach statistical significance and requires further investigation. Due to its small sample size, this study should be regarded more as hypothesis-generating.
2025-07-28 | Clinicopathological features and prognostic insights of cutaneous versus non-cutaneous angiosarcoma: A retrospective single-center cohort study.
Angiosarcoma is a rare, aggressive malignancy of endothelial origin, accounting for 1-2 % of soft tissue sarcomas. It occurs in cutaneous (C-AS) and non-cutaneous (NC-AS) forms, with distinct clinical behaviors and prognoses. While C-AS primarily affects the head and neck, NC-AS involves visceral organs such as the heart, liver, and breast. Despite advances in treatment, survival remains poor, and recurrence is common. This retrospective, single-center cohort study analyzed 30 patients diagnosed with angiosarcoma at the University Hospital Zurich (2000-2023). The study compared clinicopathological characteristics, survival outcomes, and prognostic factors influencing survival and recurrence. Patients were stratified into C-AS (n = 10) and NC-AS (n = 20) groups. Overall survival (OS) and recurrence-free survival (RFS) were assessed using Kaplan-Meier and Cox regression analyses. Both subtypes shared a poor prognosis, with an overall 5-year survival rate of 12 %. NC-AS had a higher early mortality rate, with a significantly worse median OS (9 vs. 36 months, p = 0.04), while early recurrence after treatment was more frequent in C-AS. High-grade tumor differentiation and metastases at diagnosis were independent predictors of poorer OS (p = 0.01; p = 0.04). Multimodal treatment, including surgery and radiotherapy, was associated with improved survival (p < 0.05). No clinicopathological factor showed a statistically significant association with RFS. C-AS and NC-AS exhibit distinct prognostic profiles, with NC-AS associated with a higher metastatic burden and worse outcomes. Prognostic factors such as tumor grade and metastases at diagnosis influence survival. Multimodal treatment strategies appear beneficial, though recurrence remains a major challenge. Further prospective studies are needed to refine therapeutic approaches and explore emerging targeted therapies.
cell therapies
2026-07-06 | Double free flap reconstruction using the piggyback technique for multifocal scalp radiation necrosis: a case report.
Scalp angiosarcoma is a rare, aggressive malignancy with poor prognosis, particularly when multifocal. We report a 62-year-old woman with multifocal scalp angiosarcoma, a 3.5× 3.5 cm ulcerated vertex lesion within an approximately 10× 10 cm clinically abnormal vertex field and three 1× 1 cm temporal satellite lesions (two in the right temporal region and one in the left temporal region). Initial wide excision with frozen biopsy-guided margins and reconstruction using a rotation flap and split-thickness skin grafts was followed by adjuvant radiotherapy. At 7 months after completion of radiotherapy, radiation-induced necrosis with bone exposure developed in the frontal and occipital regions, with multiple biopsies negative for recurrence. Double free flap reconstruction (radial forearm free flap and adipofascial anterolateral thigh flap using a piggyback anastomosis) was performed 11 months after radiotherapy using a single recipient vessel pair. Venous congestion on postoperative day 1 was successfully revised with vein graft interposition, resulting in complete flap survival. The patient was disease-free with stable flap coverage at the latest follow-up, more than 2.5 years after radiotherapy. This case demonstrates that double free flap reconstruction using a piggyback technique can be a safe and effective reconstructive option for extensive irradiated scalp defects in multifocal angiosarcoma.
2026-04-09 | From Palliation After Angiosarcoma Resection to Totally Autologous Aesthetic Breast Reconstruction Combining Kiss Latissimus Dorsi Flap and Contralateral Breast Sharing Internal Mammary Artery Perforator Flap: A Case Report.
Angiosarcoma of the breast is a rare but aggressive disease that often requires wide-margin resection resulting in massive thoracic defects. In this report we present the unique case of a patient who underwent primary chest wall reconstruction with palliative intent using Kiss Latissimus Dorsi (LD) Flap after resection of a huge angiosarcoma of the right breast, followed 3 years later by a secondary shift to totally autologous aesthetic breast reconstruction which was achieved by combining the first flap with breast-sharing internal mammary artery perforator (IMAP) flap and simultaneous contralateral breast reduction. The defect after extended mastectomy, measuring 24 × 18 cm, was resurfaced with a Kiss LD flap designed with two skin paddles of 24 × 13 and 14 × 5 cm, respectively. Three years after the initial reconstruction, the patient was tumor-free and required breast symmetrization. Therefore, a left reduction mammaplasty with simultaneous breast sharing Internal Mammary Artery Perforator (IMAP) flap was performed, augmenting the hypoplastic right breast with the entire lower pole of the contralateral side, transferring an 18 × 9 cm flap based on the fifth IMAP. Vascular safety of the procedure was guaranteed by intra-operative indocyanine green angiography evaluation. Recovery was uneventful and the 6 months post-operative follow-up confirmed flap integration, volume symmetry and high aesthetic satisfaction. This report underlines the versatility of this innovative combination of flaps in complex reconstructive scenarios where complex microsurgical transfers are contraindicated.
2025-11-22 | Primary cerebellar angiosarcoma: a rare case report and literature review.
Angiosarcoma is a highly aggressive malignant mesenchymal tumor, accounting for less than 1% of all soft tissue sarcomas. While most cases arise in the skin, soft tissues, liver, or heart, primary intracranial angiosarcoma (PIA) is an exceptionally rare and distinct clinicopathological entity. Due to nonspecific clinical presentations and imaging features, PIA poses significant diagnostic and therapeutic challenges. It is characterized by aggressive behavior, with high rates of recurrence and metastasis, resulting in poor overall prognosis. Here, we report a rare case of primary cerebellar angiosarcoma and review its epidemiology, pathogenesis, diagnostic considerations, and treatment strategies. A 53-year-old woman presented with progressive dizziness, occipital headache, nausea, and vomiting for five days. MRI revealed a hemorrhagic, highly vascular right cerebellar mass initially suspected to be a hemangioblastoma. Prior to surgery, her condition deteriorated, and emergency CT showed acute tumor hemorrhage, necessitating urgent resection. Intraoperatively, the tumor was highly vascular and poorly circumscribed, suggestive of a high-grade sarcoma, later confirmed as angiosarcoma. Despite gross total resection, the patient remained comatose due to brainstem compression. Follow-up CT on day 20 revealed rapid tumor recurrence. Given the poor prognosis, the family opted for palliative care, and the patient subsequently passed away. PIA is a rare and aggressive tumor with a poor prognosis, characterized by rapid progression and recurrence. Early detection and surgical resection are essential, but effective adjuvant therapies remain limited. A multidisciplinary approach is crucial to improve outcomes, and further research is needed to refine therapeutic strategies and enhance survival.
2025-02-06 | Usefulness of Dorsal Scapular Artery Perforator Flap for Donor Site Closure After Harvesting Latissimus Dorsi Flap/Thoracodorsal Artery Perforator Flap: A Report of Three Cases.
Reducing donor-site morbidity is crucial in free-flap reconstruction, with the primary goals of achieving dermis-to-dermis closure and avoiding skin grafts. Although latissimus dorsi (LD) myocutaneous and thoracodorsal artery perforator (TDAP) flaps usually allow primary closure, larger flap harvests may require skin grafts, potentially leading to undesirable outcomes. In such situations, local flap transfer can be considered for donor-site closure, yet there are few reports on this. This report aims to present cases where a dorsal scapular artery perforator (DSAP) rotational flap was used to close donor defects following large TDAP/LD flap harvests. The first case involved a 16-year-old girl who required a below-knee amputation due to an acute thrombotic event, leaving a 20 × 20 cm2-sized stump defect. Bilateral LD myocutaneous flaps were harvested, with the right donor site closed primarily, while a 20 × 9 cm2-sized defect remained on the left. A 22 × 9 cm2-sized DSAP flap, based on three perforators, was rotated to close the defect, showing excellent outcomes at 12 months. In the second and third cases, 75- and 78-year-old male patients with scalp angiosarcoma underwent wide excision and reconstruction with TDAP flaps, leaving 14 × 6 cm2 and 14 × 7 cm2-sized donor defects. DSAP flaps, 15 × 7 cm2 and 15 × 8 cm2 in size, were rotated based on nearby perforators to close these areas. Both patients showed no morbidities at postoperative 8 and 2 months, respectively. When primary closure of the donor site is challenging after harvesting large TDAP /LD flaps, a DSAP rotational flap can provide a valuable option for minimizing donor-site morbidity.
2024-09-03 | Radiation-Induced Angiosarcoma in a Patient With Klippel-Trenaunay Syndrome: A Case Report.
Klippel-Trenaunay syndrome (KTS) is a rare vascular disorder that typically presents in the lower limb with unilateral port-wine discoloration of the skin due to capillary malformations, varicose veins, and soft tissue and bone overgrowth. Radiation-induced angiosarcoma (RIAS) is a rare vascular malignancy that develops as a long-term complication secondary to radiation therapy. While there is no well-established direct relationship between KTS and development of angiosarcoma, there is literature that suggests a logical association between the 2 disorders. The present case report highlights the importance of further research into a potential connection between KTS and RIAS. A 51-year-old female with a history of KTS was referred to the plastic surgery clinic for delayed breast reconstruction following RIAS of the left breast. It was decided that a 2-stage left latissimus dorsi musculocutaneous flap reconstruction with silicone implant would best achieve her goal of symmetry. The patient reported here had an unremarkable postoperative course. Of note, this patient experienced severe body dysmorphia after her mastectomy and RIAS excision due to the absence of her left breast juxtaposed with her prior large right breast augmentation. The choice of 2-stage combined autologous/implant reconstruction likely contributed to her satisfactory cosmetic outcome. While RIAS and KTS are distinct conditions, a link may exist between the two. More research is needed to investigate this possible relationship. Aggressive treatment of RIAS is crucial for patient recovery, and a 2-stage combined autologous/implant reconstruction is an optimal choice for post-RIAS reconstruction, especially in patients hoping to achieve a large breast size.
other
2025-08-31 | Primary pulmonary artery sarcoma treated with simultaneous pulmonary valve replacement, artificial vessel replacement, and total right pneumonectomy: a case report.
Primary pulmonary artery sarcoma progresses extremely rapidly and has a poor prognosis. This condition is managed with surgical resection and multimodality therapy. However, standardized treatment is not available. A 54-year-old woman was brought to the emergency department because of chest pain and worsening dyspnea that had developed in the past month. Contrast-enhanced computed tomography scan revealed severe stenosis extending from the pulmonary artery trunk to the right pulmonary artery due to an embolic substance. Because primary pulmonary artery sarcoma was suspected, emergency surgery was performed to improve the patient's symptoms. In addition to maximal tumor resection, pulmonary artery valve replacement, artificial vessel replacement, and right total pneumonectomy were performed. Based on the assessment performed using the specimen collected perioperatively, a pathological diagnosis of angiosarcoma of the right pulmonary artery was made. The patient was discharged on postoperative day 17 with a good postoperative course. However, because of dyspnea, she was readmitted to the hospital on day 85. Tumor recurrence was noted, and chemotherapy was initiated. The patient developed cardiac failure and died on postoperative day 119. A pathological postmortem examination was performed. Metastatic lesions were found in the pericardial sac, left lung, right chest wall and pleura, and mediastinum. In the present case, postoperative recurrence was observed despite maximal resection of the surrounding tissues with tumor invasion and simultaneous reconstruction. Chemotherapy was initiated but was ineffective. Gene panel testing can help identify novel treatment options for patients with neoplastic diseases without standardized treatment. In addition, preparations should be made before surgery.
2024-11-27 | Dysregulation of miRNAs in Soft Tissue Sarcomas.
MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas-a diverse group of malignant tumors affecting soft tissues and bone sarcomas-miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.
2024-09-04 | miR-497 Target Gene Regulatory Network in Angiosarcoma.
Angiosarcoma is a vascular sarcoma that is highly aggressive and metastatic. Because of its rarity, treatment options for patients are limited. Therefore, more research is needed to identify possible therapeutic vulnerabilities. We previously found that conditional deletion of Dicer1 drives angiosarcoma development in mice. Given the role of DICER1 in canonical miRNA biogenesis, this suggests that miRNA loss is important in angiosarcoma development. After testing miRNAs previously suggested to have a tumor-suppressive role in angiosarcoma, miRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 overexpression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 in tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an angiosarcoma cell line, expression data from patients with angiosarcoma, and target prediction algorithms. We validated miR-497 direct regulation of cyclin-D2, cyclin-dependent kinase 6, and vesicle amine transport protein 1 (VAT1). One of these genes, VAT1, is an understudied protein that has been suggested to promote cell migration and metastasis in other cancers. Indeed, we find that pharmacologic inhibition of VAT1 with the natural product neocarzilin A reduces angiosarcoma migration. Implications: This work supports the potent tumor-suppressive abilities of miR-497 in angiosarcoma, providing evidence for its potential as a therapeutic agent, and provides insight into the mechanisms of tumor suppression through analysis of the target gene regulatory network of miR-497.
2024-09-04 | Clinical Pathophysiology and Research Highlights of Cardiac Angiosarcoma: Obligation for Immunogenetic Profiling to Understand Their Growth Pattern and Tailor Therapies
Cardiac angiosarcoma is the most common malignant tumor of the heart. The typical clinical profile is a young male with 30–50 years of age. Due to varied clinical presentation, it can disguise common cardiovascular disorders, such as pericarditis, congestive cardiac failure, and angina. This can delay the diagnosis, thus allowing the tumor to progress to the advanced stage by the time it is detected. Depending on tumor grade and size, a combination of surgery, chemotherapy, and radiation is advocated. Despite aggressive management, these tumors have a propensity to recur, advance, and metastasize, thereby underscoring the treatment resistance commonly encountered with these tumors. Resultantly, most of the patients are more prone to have shorter survival time, worse clinical outcomes, and grave prognosis. Research efforts should be directed toward decoding the inherent immune-genetic traits of these aggressive tumors so that their rapid progression can be extensively repressed. So, we propounded basic and clinical research studies to grasp the genetic makeup of these tumors so that crafting novel therapeutic modalities for improving prognosis and survival interval in these malignant tumors can materialize.
2020-01-23 | Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab
Patients with advanced sarcoma have limited treatment options. Talimogene laherparepvec (T-VEC) has been shown to increase tumor-specific immune activation via augmenting antigen presentation and T-cell priming. To examine whether T-VEC in combination with pembrolizumab is associated with increased tumor-infiltrating lymphocyte infiltration and programmed death-ligand 1 expression and thus with increased antitumor activity in patients with locally advanced or metastatic sarcoma. This open-label, single-institution phase 2 interventional trial of T-VEC plus pembrolizumab enrolled 20 patients with locally advanced or metastatic sarcoma between March 16 and December 4, 2017, for whom at least 1 standard systemic therapy had failed. The median duration of therapy was 16 weeks (range, 7-67 weeks). Reported analyses include data through December 14, 2018. Patients received pembrolizumab (200-mg flat dose) intravenously and T-VEC (first dose, ≤4 mL × 106plaque-forming units [PFU]/mL; second and subsequent doses, ≤4 mL × 108PFU/mL) injected into palpable tumor site(s) on day 1 of each 21-day cycle. The primary end point was objective response rate (ORR; complete response and partial response) at 24 weeks determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, criteria. Secondary end points included best ORR by immune-related RECIST criteria, progression-free survival rate at 24 weeks, overall survival, and safety. All 20 patients (12 women [60%]; median age, 63.5 years [range, 24-90 years]) were evaluable for response. The study met its primary end point of evaluating the best ORR at 24 weeks determined by RECIST, version 1.1, criteria; the best ORR was 30% (95% CI, 12%-54%; n = 6). The ORR overall was 35% (95% CI, 15%-59%; n = 7). The incidence of grade 3 treatment-related adverse events was low (4 patients [20%]). There were no grade 4 treatment-related adverse events or treatment-related deaths. In this phase 2 clinical trial, treatment with T-VEC plus pembrolizumab was associated with antitumor activity in advanced sarcoma across a range of sarcoma histologic subtypes, with a manageable safety profile. This combination therapy met its predefined primary study end point; further evaluation of T-VEC in combination with pembrolizumab for patients with select sarcoma subtypes is planned. ClinicalTrials.gov identifier:NCT03069378
small molecules
2026-08-08 | Primary adrenal epithelioid angiosarcoma: An extraordinarily rare malignancy with a challenging diagnosis.
Adrenal epithelioid angiosarcoma is an exceedingly rare vascular endothelial neoplasm, accounting for a minute fraction of sarcomas with fewer than 60 cases reported in the medical literature. We report the case of a 70-year-old female with primary adrenal epithelioid angiosarcoma, presenting with a rapidly enlarging right adrenal mass and associated severe right upper quadrant pain. Biochemical testing revealed that the mass was nonfunctional, and contrast-enhanced computed tomography revealed a large, heterogeneously enhancing lesion with inferior vena cava compression. Given rapid interval growth and severe symptoms, she underwent laparoscopic adrenalectomy, and histopathology with immunohistochemistry confirmed a diagnosis of primary adrenal epithelioid angiosarcoma. Postoperative management included paclitaxel chemotherapy, and the patient has remained disease-free for 2 years post-operation. This case emphasizes that the clinical and imaging features of adrenal epithelioid angiosarcoma are nonspecific, and definitive diagnosis requires surgical pathology with vascular marker staining to avoid misclassification as metastatic carcinoma. Timely resection in combination with chemotherapy can yield favorable outcomes despite this tumor's aggressive behavior and overall poor prognosis.
2026-08-08 | Multimodality imaging features of primary mammary angiosarcoma: a case report with delayed osseous metastases.
Primary angiosarcoma of the breast is an uncommon and aggressive vascular malignancy that typically affects young women and poses diagnostic and therapeutic challenges. We report the case of a 26-year-old nulliparous woman who presented with progressive left breast swelling over approximately 18 months. Clinical examination revealed diffuse tender swelling without skin discoloration, nipple changes, or palpable lymphadenopathy. Ultrasonography demonstrated a complex cystic mass with thick septations and increased vascularity, while mammography showed global asymmetry of the left breast without suspicious calcifications. Breast MRI revealed a large 8.4 cm heterogeneously enhancing mass in the upper outer quadrant with possible focal skin involvement, but no chest wall invasion or nodal disease. Initial staging with 18F-FDG PET/CT showed no distant metastases. The patient underwent left nipple-sparing mastectomy, and histopathological examination confirmed intermediate-grade primary mammary angiosarcoma, FNCLCC grade 2. Subsequent re-excision achieved clear surgical margins. She received adjuvant ifosfamide-epirubicin chemotherapy and radiotherapy. Initial follow-up imaging showed no residual or recurrent disease. However, 14 months after completion of treatment, follow-up 18F-FDG PET/CT demonstrated new FDG-avid lytic lesions in the sacral and iliac bones, and Breast MRI revealed a small enhancing sternal lesion, consistent with delayed osseous metastatic disease. The patient was treated with palliative radiotherapy and systemic therapy. This case highlights the diagnostic complexity of primary breast angiosarcoma, its potential for delayed hematogenous osseous spread, and the value of multimodality imaging in diagnosis, staging, treatment planning, and surveillance.
2026-08-04 | Selective Transarterial Embolization for Refractory Bleeding in Advanced Scalp Angiosarcoma: Two Cases.
Cutaneous angiosarcoma of the scalp is a highly aggressive vascular malignancy that predominantly affects elderly individuals and may cause severe tumor bleeding during disease progression. Hemorrhage from ulcerated tumors is often difficult to control, particularly in patients previously treated with chemoradiotherapy. We report two cases of advanced scalp angiosarcoma in which refractory tumor bleeding was successfully controlled by selective transarterial embolization. The first patient, a 75-year-old man with recurrent angiosarcoma of the frontal scalp region after multiple systemic therapies and radiotherapy, developed repeated arterial bleeding from ulcerated lesions requiring transfusion support. Angiography identified tumor-feeding branches of the superficial temporal artery and angular artery, and embolization achieved immediate hemostasis. A second embolization procedure was required for recurrent bleeding. The second patient, a 75-year-old woman, also developed persistent bleeding from a progressive scalp tumor despite chemoradiotherapy. Selective arterial embolization resulted in rapid and sustained bleeding control without major complications. These cases suggest that selective transarterial embolization may provide rapid control of refractory arterial tumor bleeding and reduce local treatment burden in selected patients with advanced scalp angiosarcoma.
2026-08-02 | When a haematoma is not a haematoma.
Cutaneous angiosarcoma (cAS) is a rare but highly aggressive vascular malignancy, often associated with chronic lymphoedema or previous radiotherapy. Its nonspecific clinical presentation can mimic benign conditions, leading to diagnostic delays. We report the case of a 70-year-old woman with chronic lymphoedema of the right arm following mastectomy and lymphadenectomy for breast cancer. She presented with a slowly enlarging haematoma-like lesion. Magnetic resonance imaging (MRI) performed externally suggested a benign haematoma. Due to progressive changes, the patient was referred to our department. High-resolution sonography revealed irregular dermal and subcutaneous vasculature with marked hyperperfusion. Deep skin biopsy demonstrated a vascular neoplasm composed of pleomorphic endothelial cells expressing ERG, CD31, D2-40 and c-Myc, with a high Ki-67 proliferation index, consistent with the diagnosis of cAS (Stewart-Treves syndrome). Computed tomography staging excluded metastatic disease, and systemic paclitaxel therapy was initiated. This case underlines the often inconspicuous clinical presentation of cAS and the limited diagnostic value of MRI for superficial lesions. High-resolution sonography may provide an important, noninvasive diagnostic clue by revealing marked hypervascularity, thereby prompting timely biopsy and improving early detection of this aggressive tumour.
2026-07-31 | Right atrial rupture due to cardiac angiosarcoma without haemodynamic collapse: a case report of successful multidisciplinary management.
Malignant tumours account for approximately 20%-30% of primary cardiac tumours, and reports remain rare. Cardiac angiosarcoma is a representative type, but prognosis is extremely poor: the median survival is about 4 months in unresectable cases and 14 months after complete resection [Patel SD, Peterson A, Bartczak A, Lee S, Chojnowski S, Gajewski P, et al. Med Sci Monit 2014;20:103-9].Approximately 29% of angiosarcomas present with metastasis at diagnosis, and the presence of pericardial effusion suggests pericardial invasion. Evidence regarding chemotherapy remains limited, and no standardized treatment has been established for metastatic primary cardiac tumours. We report a case of cardiac angiosarcoma in a 74-year-old man. At the time of presentation, masses were detected in the right atrium and the apex of the left ventricle. The right atrial tumour extended widely along the atrial wall and partially formed fistulous tracts, resulting in direct communication of blood flow from the right atrium into the pericardial cavity. Surgical tumour resection with atrial wall reconstruction was performed, and chemotherapy was initiated following histopathological confirmation. Due to their poor prognosis, cardiac tumours are often managed with palliative care. This case highlights two important points: first, cardiac angiosarcoma can cause atrial wall destruction and rupture, leading to direct communication between the atrium and pericardial space; second, even in cases of primary cardiac angiosarcoma with pulmonary metastases, appropriate cardiac surgery combined with chemotherapy may improve patient outcomes.
antibodies
2026-08-01 | Immune checkpoint inhibitor rechallenge after pazopanib treatment in primary pulmonary angiosarcoma: A case report.
Primary pulmonary angiosarcoma is a rare malignancy with limited therapeutic options. We report a case of primary pulmonary angiosarcoma in which tumor regression was achieved with immune checkpoint inhibitor (ICI) rechallenge following pazopanib therapy. The tumor showed strong PD-L1 expression and infiltration of CD3+, CD4+, and CD8+ T cells without CD20+ B cells. After disease control with atezolizumab, pazopanib induced tumor shrinkage but was followed by disease progression. Pembrolizumab rechallenge resulted in tumor regression and sustained benefit. This case suggests that sequential VEGF-targeted therapy and PD-1 blockade may contribute to renewed sensitivity to ICI in tumors with a T-cell-inflamed microenvironment.
2026-05-10 | The case for tumour-agnostic reimbursement of dual immunotherapy.
Barjesteh van Waalwijk van Doorn-Khosrovani and colleagues raise important questions about this recommendation for tumour-agnostic reimbursement of nivolumab and ipilimumab in Australia. We respectfully offer a counterpoint and endorse the broad coverage. In 2025, Pharmaceutical Benefits Advisory Committee (PBAC) proposed that prescribing nivolumab and ipilimumab be guided by clinical judgement informed by the best available evidence for undefined "immunotherapy-sensitive" advanced or metastatic cancers, and, in January 2026 made a similar recommendation for pembrolizumab. Patients with rare and ultra-rare cancers, including but not limited to angiosarcoma, alveolar soft part sarcoma, gestational trophoblastic disease, small cell carcinoma of the ovary (hypercalcemic type), and adrenocortical carcinoma, face profound unmet need. Within many of these diseases, a subset of patients derives substantial benefit from immunotherapy. For example, the SWOG DART (Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors) trial, the largest prospective evaluation of nivolumab plus ipilimumab in rare/ultra-rare cancers, demonstrated clinically meaningful activity across multiple histologies, without biomarker selection. Notably, some patients with metastatic disease remain disease-free years after treatment, outcomes rarely achieved with chemotherapy or supportive care in refractory settings. Therefore, concerns that biomarker-agnostic approval signals an evidentiary retreat overlook both our incomplete understanding immune sensitivity and the global access limits to comprehensive genomic testing. Importantly, clinical judgement is not arbitrary; it reflects training, experience, ethical reasoning, and patient-centred decision making. The question is whether demanding perfect evidence should prevent access to potentially transformative treatment. Grounded in evidence and expertise, PBAC's decision prioritises meaningful access to effective therapy for patients with few alternatives.
2026-05-04 | Pembrolizumab as an Off-Label Treatment of Facial Angiosarcoma: A Case Report.
of Case: We report an atypical case of cutaneous angiosarcoma presenting as unilateral nasal swelling in an elderly male. The lesion was unresponsive to topical and antibiotic therapy. Diagnosis was confirmed after surgical excision, and disease control was ultimately achieved through radiation and off-label use of pembrolizumab. Patient Info: A 79-year-old male with a history of squamous cell carcinoma presented with a 1–2 month history of erythematous, scaly swelling of the left nasal tip and ala. Family history was notable for nonmelanoma skin cancer. Initial differential diagnoses included contact dermatitis, rosacea, and rhinophyma. A shave biopsy revealed actinic damage but no malignancy. Following persistent symptoms and referral to plastic surgery, debulking surgery was performed. Histopathology confirmed cutaneous angiosarcoma. The patient declined wide local excision and instead underwent a 4-week course of hypofractionated radiation. Subsequent imaging showed regional lymph node recurrence. He declined biopsy and surgery, and was started on off-label pembrolizumab immunotherapy for disease control. Following immunotherapy, the patient experienced sustained remission with no clinical or radiographic evidence of disease four years post-treatment. Cutaneous angiosarcoma is a rare, aggressive malignancy with a poor prognosis. This case illustrates the importance of considering angiosarcoma in atypical facial lesions and demonstrates disease control using a non-traditional, patient-centered treatment strategy. Immunotherapy with pembrolizumab may offer a promising option in select patients, particularly those with contraindications to extensive surgery.
2026-03-01 | 170P AI-assisted systematic review and pooled analysis of anthracycline- versus taxane-based chemotherapy in advanced or metastatic angiosarcoma
Ridaforolimus were evaluated.PRRX1 gain and loss-of-function studies were performed in vitro and in vivo.Results: Treated tumors showed enrichment of stemness-related pathways, including epithelial-mesenchymal transition, and overexpression of SOX2, KLF4, and PRRX1, with increased Ng2+ MSC and fibroblast/chondrocyte progenitor signatures.PRRX1 knockdown reduced proliferation and increased doxorubicin sensitivity, whereas PRRX1 overexpression induced resistance in vitro and expanded the tumor-initiating cell population with a 7-fold increase in stem cell frequency by in vivo limitingdilution analysis.Treated tumors also exhibited activation of the PI3K-AKT-mTOR pathway and upregulation of IGF1 and IGF2, with elevated mTOR activity confirmed by phospho-S6 IHC.Combined IGF blockade (Xentuzumab) and mTOR inhibition (Ridaforolimus) significantly suppressed growth of chemotherapy-experienced tumors.Conclusions: CDS is driven by an undruggable fusion oncogene and rapidly develops chemoresistance.We show that chemotherapy induces IGF-PI3K-mTOR activation and a PRRX1-associated stemness program.Targeting IGF ligands and mTOR suppresses growth of chemotherapy-treated tumors, and PRRX1 acts as a key regulator of stemness and resistance.We have identified a targetable vulnerability in CDS, and further investigation of the link between IGF/mTOR signaling and PRRX1-driven stemness is required.
2026-02-16 | Postradiation angiosarcoma of the breast: a 25-year single-institution analysis of clinicopathological characteristics and immunohistochemical biomarker study.
We examined the clinicopathologic features and immunohistochemical expression of commonly tested biomarkers relevant to targeted therapy in postradiation angiosarcoma (PRAS) of the breast, aiming to better understand tumor biology and provide baseline data on tumor biomarkers to inform future therapeutic strategies for PRAS. Clinicopathologic features, outcomes, and the immunohistochemical expression of tumor biomarkers, including human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and DNA mismatch repair proteins (MMR), were analyzed in breast PRAS specimens diagnosed from 2000 to 2024. A total of 24 breast PRAS specimens from 18 patients were included in the study. All PRAS patients were female, with a median age of 72 years at the time of diagnosis. High-grade tumors were observed in 47%, 43%, and 65% of specimens according to Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC), Donnell-Rosen, and Kuba scoring methods, respectively. Surgical intervention, adjuvant chemotherapy, and radiotherapy were administered to 100%, 29%, and 23% of patients, respectively. Five patients (29%) died from the disease during a median follow-up period of 37 months. Exploratory analysis showed there was no significant association between histologic grade and overall survival, regardless of the grading system used. All PRASs were MMR-proficient with a low number of tumor-infiltrating lymphocytes (TILs) and exhibited an absence of HER2 protein expression. PD-L1 was positive in seven (32%) specimens and positively correlated with stromal TILs. Our findings suggest that breast PRAS are genomically stable and poorly immunogenic, and are likely ineligible for any HER2-targeted therapies based on current approval criteria. A subset of specimens demonstrated PD-L1 positivity, underscoring the need for further investigation of immunotherapy with anti-PD1/PD-L1 immune checkpoint inhibitors as a potential treatment option.
proteins
2026-01-29 | Hepatic Angiosarcoma Mimicking Sinusoidal Obstruction Syndrome: A Case Report.
Hepatic angiosarcoma (HAS) is an uncommon malignant tumor that is often misdiagnosed because of its nonspecific presentation and overlapping imaging findings with benign vascular tumors. Sinusoidal obstruction syndrome (SOS) is a disorder of hepatic microcirculation, usually associated with myeloablative chemotherapy and hematopoietic stem cell transplantation. The clinical and pathological overlap between SOS and hepatic angiosarcoma may complicate the diagnosis of hepatic angiosarcoma, as illustrated by this case. We report the case of a sixty-year-old man who presented to the emergency department with progressive jaundice, abdominal discomfort, and weight loss exceeding 5% of his baseline. Laboratory workup revealed a predominantly cholestatic pattern, and serologies for viral, autoimmune, and metabolic liver diseases were negative. Also, there were no known risk factors for liver disease or SOS. Repeated imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a large vascular hepatic lesion, suggestive of a benign lesion, and Doppler revealed findings compatible with SOS. Liver biopsy and hemodynamic studies indicated hepatic outflow obstruction. After clinical deterioration and expert multidisciplinary review of imaging and histology, malignant endothelial proliferation consistent with hepatic angiosarcoma was identified. Hepatic angiosarcoma can closely mimic SOS morphologically and hemodynamically. The absence of identifiable risk factors and the progressive evolution of hepatic changes should raise suspicion of malignancy, prompting multidisciplinary reassessment and careful histologic review.
2026-01-15 | Angiosarcoma developing in an ovarian fibroma: A case report.
Angiosarcomas are malignant vascular tumors primarily located in the dermis or soft tissues predominantly in the head and neck region. Ovarian localization is extremely rare, with only a few published cases. A 63-year-old patient was admitted to the hospital due to severe pain in the hypogastric and abdominal regions. The condition was interpreted as an acute abdomen and referred to surgery, and an ovarian tumor that measured 23cm×11cm×5cm and weighed 7500g was resected. Macroscopically, the cut surface showed two well-defined areas: one consisting of a matte white tissue with a fascicular appearance and firm consistency and the other hemorrhagic with necrotic areas. Histological examination revealed two patterns: one characterized by a proliferation of spindle-shaped cells without atypia, and the other by neoplastic proliferation with marked atypia, forming vascular channels or fascicles. The vascular component was positive for CD31, CD34, and ERG. The findings were interpreted as an angiosarcoma associated with a fibroma, and the patient died in the immediate postoperative period. The low incidence and ominous prognosis of primary or metastatic ovarian angiosarcomas have been confirmed. Regarding the histogenesis, a strong likelihood exists of a relationship with the ovary's rich vascular network. In both well-differentiated and poorly differentiated cases, it is crucial to consider differential diagnoses and perform immunohistochemical techniques, which can assist in achieving an accurate diagnosis. The association between fibroma and angiosarcoma is poorly understood and the histogenesis remains unclear.
2026-01-07 | Adult urologic sarcomas: a single institution experience over 25 years.
Genitourinary (GU) sarcomas are rare soft tissue malignancies, comprising around 2% of all GU cancers. Due to their rarity, limited data exist on optimal management and long-term outcomes. This study presents a 25-year single-institution experience, evaluating clinical presentation, treatment strategies, and survival outcomes, aims to identify trends over time and potential predictors of prognosis. A retrospective review was conducted of patients aged ≥18 years diagnosed with GU sarcomas at the University of Iowa Hospitals and Clinics (1998-2023). Data on tumor subtype, staging, histopathology, treatment modalities, and survival outcomes were analyzed. Kaplan-Meier analysis estimated recurrence-free survival (RFS) and overall survival (OS). Among 33 cases, the most common presentations in order of frequency were liposarcoma (LPS) (n = 15), leiomyosarcoma (LMS) (n = 12), rhabdomyosarcoma (RMS) (n = 5), and angiosarcoma (n = 1). Paratesticular tumors (n = 23) were most frequent, followed by bladder (n = 5), prostate (n = 2), and kidney (n = 2). The median age was 51 for LMS, 60 for LPS, and 24 for RMS. LMS had higher stage (66.67%), grade (83.33%), recurrence (25.00%), and mortality (41.67%) rates compared to LPS (recurrence: 13.33%, mortality: 20.00%). At 36 months, RFS was 63% (95% CI: 39%-79%), and OS was 81% (95% CI: 57%-92%) for the entire cohort. Follow-up duration was 19.9 months for LMS and 33.8 months for LPS. Surgical resection remains the mainstay of treatment for GU sarcomas. Margin status, tumor grade, and size are key prognostic factors. LMS carries the highest recurrence risk, and RMS exhibits aggressive progression. Further investigation into targeted therapies is warranted to improve outcomes.
2025-10-20 | Characteristics, Outcomes, and Risk Factors in Primary and Secondary Angiosarcoma: A Retrospective Cohort Study.
Angiosarcomas (ASs) are a heterogeneous subtype of soft tissue sarcomas. They can be subdivided into primary and secondary AS, with secondary AS being predominant, particularly those following radiotherapy. The aim of this study was first to analyze our patient cohort on a descriptive level and then to identify possible risk factors with regard to one and 5-year survival using logistic regression. The study was designed as a retrospective, single-center cohort study. All patients with histologically confirmed AS over 18 years of age were included in the study. Binary logistic regression was used for univariate analysis screening of continuous or dichotomous variables, respectively. For multivariate analysis, binary multivariate logistic regression was performed to assess independent associations between chosen variables and AS. A total of 39 patients were included in this study. 14 (35.9%) had primary and 25 (64%) had secondary AS. Women were more frequently affected (76.9%) than men (23.1%). The 1-year survival rate was 87.2%, and the 5-year survival rate was 51.3%. In the logistic regression analyses, nicotine consumption and a history of carcinoma were identified as significant factors influencing the 1-year survival rate. For the 5-year survival rate, only breast cancer was found to be a significant influencing factor in the univariate analysis. Based on univariate logistic regression, all variables with a p value of < 0.1 were chosen to be included into multivariate analysis. The multivariate analysis showed diabetes mellitus (p=0.067) with an association to influence the 5-year survival rate. We were able to show that the proportion of secondary ASs is predominant. These occur after radiation treatment of the breast. Diabetes mellitus may be associated with reduced 5-year survival, although this finding did not reach statistical significance and requires further investigation. Due to its small sample size, this study should be regarded more as hypothesis-generating.
2025-07-28 | Clinicopathological features and prognostic insights of cutaneous versus non-cutaneous angiosarcoma: A retrospective single-center cohort study.
Angiosarcoma is a rare, aggressive malignancy of endothelial origin, accounting for 1-2 % of soft tissue sarcomas. It occurs in cutaneous (C-AS) and non-cutaneous (NC-AS) forms, with distinct clinical behaviors and prognoses. While C-AS primarily affects the head and neck, NC-AS involves visceral organs such as the heart, liver, and breast. Despite advances in treatment, survival remains poor, and recurrence is common. This retrospective, single-center cohort study analyzed 30 patients diagnosed with angiosarcoma at the University Hospital Zurich (2000-2023). The study compared clinicopathological characteristics, survival outcomes, and prognostic factors influencing survival and recurrence. Patients were stratified into C-AS (n = 10) and NC-AS (n = 20) groups. Overall survival (OS) and recurrence-free survival (RFS) were assessed using Kaplan-Meier and Cox regression analyses. Both subtypes shared a poor prognosis, with an overall 5-year survival rate of 12 %. NC-AS had a higher early mortality rate, with a significantly worse median OS (9 vs. 36 months, p = 0.04), while early recurrence after treatment was more frequent in C-AS. High-grade tumor differentiation and metastases at diagnosis were independent predictors of poorer OS (p = 0.01; p = 0.04). Multimodal treatment, including surgery and radiotherapy, was associated with improved survival (p < 0.05). No clinicopathological factor showed a statistically significant association with RFS. C-AS and NC-AS exhibit distinct prognostic profiles, with NC-AS associated with a higher metastatic burden and worse outcomes. Prognostic factors such as tumor grade and metastases at diagnosis influence survival. Multimodal treatment strategies appear beneficial, though recurrence remains a major challenge. Further prospective studies are needed to refine therapeutic approaches and explore emerging targeted therapies.
cell therapies
2026-07-06 | Double free flap reconstruction using the piggyback technique for multifocal scalp radiation necrosis: a case report.
Scalp angiosarcoma is a rare, aggressive malignancy with poor prognosis, particularly when multifocal. We report a 62-year-old woman with multifocal scalp angiosarcoma, a 3.5× 3.5 cm ulcerated vertex lesion within an approximately 10× 10 cm clinically abnormal vertex field and three 1× 1 cm temporal satellite lesions (two in the right temporal region and one in the left temporal region). Initial wide excision with frozen biopsy-guided margins and reconstruction using a rotation flap and split-thickness skin grafts was followed by adjuvant radiotherapy. At 7 months after completion of radiotherapy, radiation-induced necrosis with bone exposure developed in the frontal and occipital regions, with multiple biopsies negative for recurrence. Double free flap reconstruction (radial forearm free flap and adipofascial anterolateral thigh flap using a piggyback anastomosis) was performed 11 months after radiotherapy using a single recipient vessel pair. Venous congestion on postoperative day 1 was successfully revised with vein graft interposition, resulting in complete flap survival. The patient was disease-free with stable flap coverage at the latest follow-up, more than 2.5 years after radiotherapy. This case demonstrates that double free flap reconstruction using a piggyback technique can be a safe and effective reconstructive option for extensive irradiated scalp defects in multifocal angiosarcoma.
2026-04-09 | From Palliation After Angiosarcoma Resection to Totally Autologous Aesthetic Breast Reconstruction Combining Kiss Latissimus Dorsi Flap and Contralateral Breast Sharing Internal Mammary Artery Perforator Flap: A Case Report.
Angiosarcoma of the breast is a rare but aggressive disease that often requires wide-margin resection resulting in massive thoracic defects. In this report we present the unique case of a patient who underwent primary chest wall reconstruction with palliative intent using Kiss Latissimus Dorsi (LD) Flap after resection of a huge angiosarcoma of the right breast, followed 3 years later by a secondary shift to totally autologous aesthetic breast reconstruction which was achieved by combining the first flap with breast-sharing internal mammary artery perforator (IMAP) flap and simultaneous contralateral breast reduction. The defect after extended mastectomy, measuring 24 × 18 cm, was resurfaced with a Kiss LD flap designed with two skin paddles of 24 × 13 and 14 × 5 cm, respectively. Three years after the initial reconstruction, the patient was tumor-free and required breast symmetrization. Therefore, a left reduction mammaplasty with simultaneous breast sharing Internal Mammary Artery Perforator (IMAP) flap was performed, augmenting the hypoplastic right breast with the entire lower pole of the contralateral side, transferring an 18 × 9 cm flap based on the fifth IMAP. Vascular safety of the procedure was guaranteed by intra-operative indocyanine green angiography evaluation. Recovery was uneventful and the 6 months post-operative follow-up confirmed flap integration, volume symmetry and high aesthetic satisfaction. This report underlines the versatility of this innovative combination of flaps in complex reconstructive scenarios where complex microsurgical transfers are contraindicated.
2025-11-22 | Primary cerebellar angiosarcoma: a rare case report and literature review.
Angiosarcoma is a highly aggressive malignant mesenchymal tumor, accounting for less than 1% of all soft tissue sarcomas. While most cases arise in the skin, soft tissues, liver, or heart, primary intracranial angiosarcoma (PIA) is an exceptionally rare and distinct clinicopathological entity. Due to nonspecific clinical presentations and imaging features, PIA poses significant diagnostic and therapeutic challenges. It is characterized by aggressive behavior, with high rates of recurrence and metastasis, resulting in poor overall prognosis. Here, we report a rare case of primary cerebellar angiosarcoma and review its epidemiology, pathogenesis, diagnostic considerations, and treatment strategies. A 53-year-old woman presented with progressive dizziness, occipital headache, nausea, and vomiting for five days. MRI revealed a hemorrhagic, highly vascular right cerebellar mass initially suspected to be a hemangioblastoma. Prior to surgery, her condition deteriorated, and emergency CT showed acute tumor hemorrhage, necessitating urgent resection. Intraoperatively, the tumor was highly vascular and poorly circumscribed, suggestive of a high-grade sarcoma, later confirmed as angiosarcoma. Despite gross total resection, the patient remained comatose due to brainstem compression. Follow-up CT on day 20 revealed rapid tumor recurrence. Given the poor prognosis, the family opted for palliative care, and the patient subsequently passed away. PIA is a rare and aggressive tumor with a poor prognosis, characterized by rapid progression and recurrence. Early detection and surgical resection are essential, but effective adjuvant therapies remain limited. A multidisciplinary approach is crucial to improve outcomes, and further research is needed to refine therapeutic strategies and enhance survival.
2025-02-06 | Usefulness of Dorsal Scapular Artery Perforator Flap for Donor Site Closure After Harvesting Latissimus Dorsi Flap/Thoracodorsal Artery Perforator Flap: A Report of Three Cases.
Reducing donor-site morbidity is crucial in free-flap reconstruction, with the primary goals of achieving dermis-to-dermis closure and avoiding skin grafts. Although latissimus dorsi (LD) myocutaneous and thoracodorsal artery perforator (TDAP) flaps usually allow primary closure, larger flap harvests may require skin grafts, potentially leading to undesirable outcomes. In such situations, local flap transfer can be considered for donor-site closure, yet there are few reports on this. This report aims to present cases where a dorsal scapular artery perforator (DSAP) rotational flap was used to close donor defects following large TDAP/LD flap harvests. The first case involved a 16-year-old girl who required a below-knee amputation due to an acute thrombotic event, leaving a 20 × 20 cm2-sized stump defect. Bilateral LD myocutaneous flaps were harvested, with the right donor site closed primarily, while a 20 × 9 cm2-sized defect remained on the left. A 22 × 9 cm2-sized DSAP flap, based on three perforators, was rotated to close the defect, showing excellent outcomes at 12 months. In the second and third cases, 75- and 78-year-old male patients with scalp angiosarcoma underwent wide excision and reconstruction with TDAP flaps, leaving 14 × 6 cm2 and 14 × 7 cm2-sized donor defects. DSAP flaps, 15 × 7 cm2 and 15 × 8 cm2 in size, were rotated based on nearby perforators to close these areas. Both patients showed no morbidities at postoperative 8 and 2 months, respectively. When primary closure of the donor site is challenging after harvesting large TDAP /LD flaps, a DSAP rotational flap can provide a valuable option for minimizing donor-site morbidity.
2024-09-03 | Radiation-Induced Angiosarcoma in a Patient With Klippel-Trenaunay Syndrome: A Case Report.
Klippel-Trenaunay syndrome (KTS) is a rare vascular disorder that typically presents in the lower limb with unilateral port-wine discoloration of the skin due to capillary malformations, varicose veins, and soft tissue and bone overgrowth. Radiation-induced angiosarcoma (RIAS) is a rare vascular malignancy that develops as a long-term complication secondary to radiation therapy. While there is no well-established direct relationship between KTS and development of angiosarcoma, there is literature that suggests a logical association between the 2 disorders. The present case report highlights the importance of further research into a potential connection between KTS and RIAS. A 51-year-old female with a history of KTS was referred to the plastic surgery clinic for delayed breast reconstruction following RIAS of the left breast. It was decided that a 2-stage left latissimus dorsi musculocutaneous flap reconstruction with silicone implant would best achieve her goal of symmetry. The patient reported here had an unremarkable postoperative course. Of note, this patient experienced severe body dysmorphia after her mastectomy and RIAS excision due to the absence of her left breast juxtaposed with her prior large right breast augmentation. The choice of 2-stage combined autologous/implant reconstruction likely contributed to her satisfactory cosmetic outcome. While RIAS and KTS are distinct conditions, a link may exist between the two. More research is needed to investigate this possible relationship. Aggressive treatment of RIAS is crucial for patient recovery, and a 2-stage combined autologous/implant reconstruction is an optimal choice for post-RIAS reconstruction, especially in patients hoping to achieve a large breast size.
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2025-08-31 | Primary pulmonary artery sarcoma treated with simultaneous pulmonary valve replacement, artificial vessel replacement, and total right pneumonectomy: a case report.
Primary pulmonary artery sarcoma progresses extremely rapidly and has a poor prognosis. This condition is managed with surgical resection and multimodality therapy. However, standardized treatment is not available. A 54-year-old woman was brought to the emergency department because of chest pain and worsening dyspnea that had developed in the past month. Contrast-enhanced computed tomography scan revealed severe stenosis extending from the pulmonary artery trunk to the right pulmonary artery due to an embolic substance. Because primary pulmonary artery sarcoma was suspected, emergency surgery was performed to improve the patient's symptoms. In addition to maximal tumor resection, pulmonary artery valve replacement, artificial vessel replacement, and right total pneumonectomy were performed. Based on the assessment performed using the specimen collected perioperatively, a pathological diagnosis of angiosarcoma of the right pulmonary artery was made. The patient was discharged on postoperative day 17 with a good postoperative course. However, because of dyspnea, she was readmitted to the hospital on day 85. Tumor recurrence was noted, and chemotherapy was initiated. The patient developed cardiac failure and died on postoperative day 119. A pathological postmortem examination was performed. Metastatic lesions were found in the pericardial sac, left lung, right chest wall and pleura, and mediastinum. In the present case, postoperative recurrence was observed despite maximal resection of the surrounding tissues with tumor invasion and simultaneous reconstruction. Chemotherapy was initiated but was ineffective. Gene panel testing can help identify novel treatment options for patients with neoplastic diseases without standardized treatment. In addition, preparations should be made before surgery.
2024-11-27 | Dysregulation of miRNAs in Soft Tissue Sarcomas.
MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas-a diverse group of malignant tumors affecting soft tissues and bone sarcomas-miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.
2024-09-04 | miR-497 Target Gene Regulatory Network in Angiosarcoma.
Angiosarcoma is a vascular sarcoma that is highly aggressive and metastatic. Because of its rarity, treatment options for patients are limited. Therefore, more research is needed to identify possible therapeutic vulnerabilities. We previously found that conditional deletion of Dicer1 drives angiosarcoma development in mice. Given the role of DICER1 in canonical miRNA biogenesis, this suggests that miRNA loss is important in angiosarcoma development. After testing miRNAs previously suggested to have a tumor-suppressive role in angiosarcoma, miRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 overexpression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 in tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an angiosarcoma cell line, expression data from patients with angiosarcoma, and target prediction algorithms. We validated miR-497 direct regulation of cyclin-D2, cyclin-dependent kinase 6, and vesicle amine transport protein 1 (VAT1). One of these genes, VAT1, is an understudied protein that has been suggested to promote cell migration and metastasis in other cancers. Indeed, we find that pharmacologic inhibition of VAT1 with the natural product neocarzilin A reduces angiosarcoma migration. Implications: This work supports the potent tumor-suppressive abilities of miR-497 in angiosarcoma, providing evidence for its potential as a therapeutic agent, and provides insight into the mechanisms of tumor suppression through analysis of the target gene regulatory network of miR-497.
2024-09-04 | Clinical Pathophysiology and Research Highlights of Cardiac Angiosarcoma: Obligation for Immunogenetic Profiling to Understand Their Growth Pattern and Tailor Therapies
Cardiac angiosarcoma is the most common malignant tumor of the heart. The typical clinical profile is a young male with 30–50 years of age. Due to varied clinical presentation, it can disguise common cardiovascular disorders, such as pericarditis, congestive cardiac failure, and angina. This can delay the diagnosis, thus allowing the tumor to progress to the advanced stage by the time it is detected. Depending on tumor grade and size, a combination of surgery, chemotherapy, and radiation is advocated. Despite aggressive management, these tumors have a propensity to recur, advance, and metastasize, thereby underscoring the treatment resistance commonly encountered with these tumors. Resultantly, most of the patients are more prone to have shorter survival time, worse clinical outcomes, and grave prognosis. Research efforts should be directed toward decoding the inherent immune-genetic traits of these aggressive tumors so that their rapid progression can be extensively repressed. So, we propounded basic and clinical research studies to grasp the genetic makeup of these tumors so that crafting novel therapeutic modalities for improving prognosis and survival interval in these malignant tumors can materialize.
2020-01-23 | Objective Response Rate Among Patients With Locally Advanced or Metastatic Sarcoma Treated With Talimogene Laherparepvec in Combination With Pembrolizumab
Patients with advanced sarcoma have limited treatment options. Talimogene laherparepvec (T-VEC) has been shown to increase tumor-specific immune activation via augmenting antigen presentation and T-cell priming. To examine whether T-VEC in combination with pembrolizumab is associated with increased tumor-infiltrating lymphocyte infiltration and programmed death-ligand 1 expression and thus with increased antitumor activity in patients with locally advanced or metastatic sarcoma. This open-label, single-institution phase 2 interventional trial of T-VEC plus pembrolizumab enrolled 20 patients with locally advanced or metastatic sarcoma between March 16 and December 4, 2017, for whom at least 1 standard systemic therapy had failed. The median duration of therapy was 16 weeks (range, 7-67 weeks). Reported analyses include data through December 14, 2018. Patients received pembrolizumab (200-mg flat dose) intravenously and T-VEC (first dose, ≤4 mL × 106plaque-forming units [PFU]/mL; second and subsequent doses, ≤4 mL × 108PFU/mL) injected into palpable tumor site(s) on day 1 of each 21-day cycle. The primary end point was objective response rate (ORR; complete response and partial response) at 24 weeks determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, criteria. Secondary end points included best ORR by immune-related RECIST criteria, progression-free survival rate at 24 weeks, overall survival, and safety. All 20 patients (12 women [60%]; median age, 63.5 years [range, 24-90 years]) were evaluable for response. The study met its primary end point of evaluating the best ORR at 24 weeks determined by RECIST, version 1.1, criteria; the best ORR was 30% (95% CI, 12%-54%; n = 6). The ORR overall was 35% (95% CI, 15%-59%; n = 7). The incidence of grade 3 treatment-related adverse events was low (4 patients [20%]). There were no grade 4 treatment-related adverse events or treatment-related deaths. In this phase 2 clinical trial, treatment with T-VEC plus pembrolizumab was associated with antitumor activity in advanced sarcoma across a range of sarcoma histologic subtypes, with a manageable safety profile. This combination therapy met its predefined primary study end point; further evaluation of T-VEC in combination with pembrolizumab for patients with select sarcoma subtypes is planned. ClinicalTrials.gov identifier:NCT03069378
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Drug Discovery Landscape
3 orphan drug designations for Angiosarcoma.
3 orphan drug designations for Angiosarcoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Oraxol | small molecules | FDA | 2018-04-16 | — | Health Hope Pharma |
PEG-b-PLA micelles containing (1) paclitaxel, (2) sirolimus (rapamycin) and (3) tanespimycin (17-AAG)(also known as: triolimus) | small molecules | FDA | 2015-04-02 | — | Co-D Therapeutics, Inc. |
Human anti-integrin receptor av monoclonal antibody | antibodies | FDA | 2005-05-05 | — | Janssen Research & Development, LLC |
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