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Cross-provider research synthesis

Angiosarcoma

MONDO:0016982 Curated 2026-07-04T00:00:00Z 9 harmonized findings
falcon · 32 citations openscientist · 56 citations
Concordant asserts the finding Partial supports a weaker/qualified form Contradictory conflicts with it Silent does not address it

Harmonized findings

Angiosarcoma is a rare, aggressive malignancy of vascular endothelial origin in which dysregulated angiogenesis/lymphangiogenesis is the central pathologic program, with marked biologic heterogeneity across anatomic sites and etiologies.

UNANIMOUS INTEGRATED
pathophysiology
ProviderStanceScoreEvidence
falcon CONCORDANT 95% Angiosarcoma is an endothelial malignancy in which dysregulated angiogenesis/lymphangiogenesis is central.
Falcon frames angiosarcoma as an endothelial malignancy centered on dysregulated angiogenesis/lymphangiogenesis.
DOI:10.3390/cancers12113321
openscientist CONCORDANT 90% Angiosarcoma is a malignant mesenchymal neoplasm of endothelial cell origin that phenotypically and functionally recapitulates normal endothelium
OpenScientist independently defines angiosarcoma as an endothelial-origin malignancy that recapitulates normal endothelium.
PMID:38391320

Radiation-associated (secondary) angiosarcoma is molecularly defined by near-universal high-level MYC amplification (8q24), frequently with FLT4 (VEGFR3) coamplification, which distinguishes it from primary angiosarcoma and serves as a diagnostic biomarker.

UNANIMOUS INTEGRATED
genetic_factordiagnosis
ProviderStanceScoreEvidence
falcon CONCORDANT 90% a large molecular cohort quantified near-ubiquitous MYC amplification in radiation-associated breast angiosarcoma (91.8%)
Falcon reports near-ubiquitous MYC amplification (91.8%) in radiation-associated breast angiosarcoma and notes frequent FLT4 co-amplification.
DOI:10.1002/gcc.23240
openscientist CONCORDANT 95% High-level MYC amplification was found in 100% of secondary AS, but in none of the AVL or other radiation-associated sarcomas. Coamplification of FLT4 (encoding VEGFR3) was identified in 25% of secondary AS.
OpenScientist quotes MYC amplification in 100% of secondary AS with 25% FLT4 coamplification; the higher figure reflects an all-secondary-AS denominator versus Falcon's breast-only cohort — a coverage difference, not a conflict.
PMID:20949568

Primary/sporadic angiosarcoma (especially primary breast) is driven by recurrent activating alterations in angiogenic-signaling genes — KDR (VEGFR2), PIK3CA, and PTPRB — at higher frequency than in angiosarcoma overall.

UNANIMOUS INTEGRATED
genetic_factor
ProviderStanceScoreEvidence
falcon CONCORDANT 85% Angiosarcoma Project WES found primary breast angiosarcoma significantly enriched for PIK3CA mutations (9/18 vs 1/29; p=0.0003).
Falcon documents KDR and PIK3CA enrichment (and PTPRB loss-of-function) concentrated in primary breast angiosarcoma; the quote captures the PIK3CA enrichment statistic.
DOI:10.1038/s41591-019-0749-z
openscientist CONCORDANT 95% Recurrent genomic alterations were identified in KDR (70%), PIK3CA/PIK3R1 (70%), and PTPRB (30%), each at higher frequencies than reported in AS across all sites.
OpenScientist enumerates all three drivers (KDR, PIK3CA, PTPRB) with frequencies in primary mammary angiosarcoma.
PMID:32123305

UV-associated cutaneous head-and-neck angiosarcoma carries a UV mutational signature and a high tumor mutational burden, defining an immunogenic, hypermutated subtype.

UNANIMOUS INTEGRATED
genetic_factorpathophysiology
ProviderStanceScoreEvidence
falcon CONCORDANT 90% HNFS tumors had much higher median TMB (20.7 muts/Mb vs 2.8 non-HNFS) and a dominant UV mutational signature in 10/12 HNFS samples.
Falcon reports the UV mutational signature and markedly elevated TMB in head/neck/face/scalp (HNFS) cutaneous angiosarcoma.
DOI:10.1038/s41591-019-0749-z
openscientist CONCORDANT 90% Head and neck angiosarcomas in sun-exposed skin carry UV mutational signatures (SBS7), with UV-positive cases harboring significantly higher tumor mutational burden than UV-negative cases (P = 0.0294)
OpenScientist names the UV signature (SBS7) and the significantly higher TMB in UV-positive head/neck angiosarcoma.
PMID:37106027

Across etiologic subtypes, angiosarcoma signaling converges on downstream pro-proliferative/survival cascades — notably PI3K/AKT/mTOR and RAS-MAPK — downstream of endothelial receptor tyrosine kinase activation.

UNANIMOUS INTEGRATED
pathophysiologygene_function
ProviderStanceScoreEvidence
falcon CONCORDANT 85% driven by VEGF receptor activation and downstream PI3K/MAPK cascades.
Falcon states that endothelial proliferation/migration is driven by VEGF receptor activation and downstream PI3K/MAPK cascades, and elsewhere that signaling converges on MAPK and PI3K/AKT/mTOR across subtypes.
DOI:10.7759/cureus.41947
openscientist CONCORDANT 85% Angiosarcoma pathogenesis involves convergent activation of several key signaling cascades:
OpenScientist frames pathogenesis as convergent activation of key cascades (VEGF/VEGFR, PI3K-AKT-mTOR, RAS-MAPK, MYC) that it then enumerates.
PMID:23938603

Immune checkpoint inhibitors show meaningful clinical activity in angiosarcoma, particularly in the UV- and radiation-associated, high-TMB subtypes.

UNANIMOUS INTEGRATED
treatment
ProviderStanceScoreEvidence
falcon CONCORDANT 80% pembrolizumab and other anti–PD-1/PD-L1 regimens show notable activity in select cutaneous/UV-high disease and variable responses otherwise.
Falcon reports checkpoint-inhibitor activity concentrated in cutaneous/UV-high disease with variable responses otherwise, but predates and omits the specific modern trials.
DOI:10.1038/s41591-019-0749-z
openscientist CONCORDANT 90% Immune checkpoint inhibitors demonstrate meaningful activity in angiosarcoma, particularly in UV- and radiation-associated subtypes.
OpenScientist adds detailed trial evidence (CEMangio cemiplimab ORR 27.8%; cabozantinib+nivolumab ORR 59%) supporting ICI activity, especially in UV/radiation subtypes.
PMID:40632032, PMID:40056281

Angiosarcoma incidence has been rising, driven substantially by secondary breast/chest-wall (radiation-associated) disease.

UNANIMOUS INTEGRATED
epidemiology
ProviderStanceScoreEvidence
falcon CONCORDANT 70% secondary breast angiosarcoma incidence rising
Falcon reports overall angiosarcoma incidence doubling (2001-2019) with rising secondary breast angiosarcoma driven by breast irradiation.
DOI:10.1001/jamanetworkopen.2024.6235
openscientist CONCORDANT 85% The incidence of secondary breast angiosarcoma increased 3-fold from approximately 10 to 30 cases per 100,000 person-years between 1992 and 2016 (P = 0.0037)
OpenScientist quantifies a 3-fold rise in secondary breast angiosarcoma incidence.
PMID:37725702

Angiosarcoma carries a poor overall prognosis, with 5-year survival on the order of ~25-35% and worse outcomes for non-cutaneous/visceral disease.

MAJORITY INTEGRATED
prognosis
ProviderStanceScoreEvidence
openscientist CONCORDANT 90% overall 5-year survival rate of approximately 26.7% (95% CI 25.4–28.1%) based on SEER database analysis of 5,135 patients
OpenScientist gives a population-level SEER 5-year overall survival of 26.7% and details site-dependent survival differences.
PMID:35478727
falcon PARTIAL 50% with poor prognosis overall; cutaneous angiosarcoma review reports mean 5-year survival ~33.5%.
Falcon agrees prognosis is poor but cites a cutaneous-only 5-year survival (~33.5%) rather than an overall SEER figure — a different denominator, not a contradiction.
DOI:10.3389/fmed.2023.1090168

Canine (spontaneous) hemangiosarcoma is a comparative One Health model that shares angiosarcoma driver mutations (PIK3CA, TP53, NRAS), supporting cross-species therapeutic development.

SINGLE LEAD
genetic_factor
ProviderStanceScoreEvidence
openscientist CONCORDANT 90% Overall, we identified potential driver mutations in over 90% of the cases, including well-documented (in human cancers) oncogenic mutations in PIK3CA (46%), PTEN (6%), PLCG1(4%), and TP53 (66%), as well as previously undetected recurrent activating mutations in NRAS (24%)
OpenScientist devotes dedicated Other Species and Model Organism sections to canine hemangiosarcoma, quoting the shared driver-mutation landscape.
PMID:32210430
falcon SILENT —
Falcon's pathophysiology-focused human report does not address canine hemangiosarcoma or comparative animal models.

Narrative

Overview

Both providers frame angiosarcoma as a rare, aggressive endothelial malignancy best understood as a set of molecularly distinct etiologic subtypes (primary/sporadic, radiation-associated, UV head/neck, chemical hepatic, chronic-lymphedema) unified by dysregulated angiogenesis and endothelial receptor signaling. Falcon is a focused pathophysiology/molecular report; OpenScientist is a comprehensive, 15-domain characterization that additionally covers diagnostics, prognosis, treatment trials, and a canine comparative model.

Agreement

The reports converge strongly on the core biology: endothelial cell of origin with dysregulated angiogenesis; near-universal MYC amplification (with frequent FLT4 coamplification) defining radiation-associated disease; KDR, PIK3CA, and PTPRB activation in primary/sporadic (especially breast) angiosarcoma; a UV mutational signature with high TMB in head/neck cutaneous disease; convergence on PI3K/AKT/mTOR and RAS-MAPK signaling; rising incidence driven by secondary breast/chest-wall disease; poor overall prognosis; and immune checkpoint inhibitor activity concentrated in UV/radiation high-TMB subtypes.

Divergence

Divergence is coverage and recency rather than conflict. OpenScientist adds substantial breadth Falcon lacks: comprehensive survival statistics (SEER 5-year OS 26.7%), a full diagnostic IHC panel (CD31/ERG/MYC), modern immunotherapy trials (CEMangio cemiplimab, cabozantinib+nivolumab), hepatic chemical-carcinogen etiologies (vinyl chloride, thorotrast, arsenic, aristolochic acid), germline predisposition (Li-Fraumeni/CHEK2/xeroderma pigmentosum), and an extensive canine hemangiosarcoma model section on which Falcon is entirely silent. The only numeric differences (MYC 91.8% breast vs 100% secondary; 5-year survival ~33.5% cutaneous vs 26.7% overall) reflect different denominators, not contradictions.

Integration

The concordant mechanistic and genetic findings (endothelial/angiogenic core; MYC-amplified radiation-associated program; KDR/PIK3CA/PTPRB primary drivers; UV-hypermutation subtype; downstream PI3K-AKT-mTOR/MAPK convergence), epidemiology (rising secondary breast incidence), prognosis, and ICI activity are suitable for integration into kb/disorders/Angiosarcoma.yaml as curated pathophysiology, genetic, epidemiology, prognosis, and treatment content.

Not integrated (leads)

The canine hemangiosarcoma comparative model is retained as a research lead rather than promoted as human disease content, since dismech section tags do not include a model-organism category. OpenScientist's investigational treatment leads (photodynamic therapy, anti-SFRP2, CDK4/6 inhibitors, vaccine approaches) similarly remain leads pending curated evidence verification.

Cross-provider synthesis comparing falcon (pathophysiology-focused) and openscientist (comprehensive, 15-domain) deep-research reports on Angiosarcoma. No genuine contradictions were found; divergence is coverage/recency plus denominator-driven numeric differences. best_matching_text values are verbatim excerpts from the two report files. Literature evidence snippets were left to the main curation pipeline; only per-provider citations are retained here.