Optimal Clinical Management and the Molecular Biology of Angiosarcomas

Chen, Tom Wei‐Wu; Burns, Jessica; Jones, Robin L.; Huang, Paul H.

doi:10.3390/cancers12113321

Cited by 16 publications

(32 citation statements)

References 132 publications

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“…Other investigations have also reported frequent TP53 mutations in human angiosarcomas. [ 7 – 9 ] Collectively, these genetic studies strongly suggest that the PI3K, MAPK, and TP53 pathways play an important role in the development of angiosarcoma. In addition, Chadwick et al reported that PTEN was largely absent in high-grade angiosarcomas, while pMAPK was activated in all tumors of vascular origin.…”

Section: Discussionmentioning

confidence: 99%

Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma

Wan

Zhang

et al. 2021

Medicine

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Angiosarcoma is a rare, highly aggressive malignant tumor originating from endothelial cells that line the lumen of blood or lymphatic vessels. The molecular mechanisms of scalp and face angiosarcoma still need to be elucidated. This study aimed to investigate the expression of phosphatase and tensin homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphorylated mitogen-activated kinase-like protein (pMAPK), and tumor protein p53 (TP53) in scalp and face angiosarcoma and to assess tumor tissue apoptosis.The expression and intracellular distribution of PTEN, PIK3CA, pMAPK, and TP53 proteins in 21 specimens of human scalp and face angiosarcoma and 16 specimens of human benign hemangioma were evaluated using immunohistochemistry. Tumor cell apoptosis was assessed by terminal deoxyribonucleotide transferase-mediated dUTP nick end-labeling staining.Significantly lower PTEN but higher PIK3CA, pMAPK, and TP53 immunostaining were detected in the angiosarcoma specimens than in the benign hemangioma specimens(P < .01). The angiosarcoma tissues exhibited significantly higher apoptosis indices than the benign hemangioma tissues (P < .01). The positive expression rates of PIK3CA, pMAPK, and TP53 were correlated with the degree of tumor differentiation in the human scalp and face angiosarcoma.The PI3K, MAPK, and TP53 pathways might be involved in angiosarcoma tumorigenesis in humans and may serve as therapeutic targets for the effective treatment of this malignancy.

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Section: Discussionmentioning

confidence: 99%

Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma

Wan

Zhang

et al. 2021

Medicine

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“…On the other hand, recent case series have suggested that immune checkpoint inhibitors may be active in the treatment of advanced AS [ 15 ], while the combination of VEGFR and checkpoint inhibitors, already established in the treatment of several solid tumors, also appears to be a promising treatment option in soft tissue sarcoma patients in general [ 16 ]. We therefore believe that future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting, as is the case in the currently recruiting NCT04339738 trial [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

Pink

Andreou

Bauer

et al. 2021

Cancers

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We aimed to evaluate the efficacy and toxicity of paclitaxel combined with pazopanib in advanced angiosarcoma (AS). The primary end point was progression-free survival (PFS) rate at six months (PFSR6). Planned accrual was 44 patients in order to detect a PFSR6 of >55%, with an interim futility analysis of the first 14 patients. The study did not meet its predetermined interim target of 6/14 patients progression-free at 6 months. At the time of this finding, 26 patients had been enrolled between July 2014 and April 2016, resulting in an overrunning of 12 patients. After a median follow-up of 9.5 (IQR 7.7–15.4) months, PFSR6 amounted to 46%. Two patients had a complete and seven patients a partial response. Patients with superficial AS had a significantly higher PFSR6 (61% vs. 13%, p = 0.0247) and PFS (11.3 vs. 2.7 months, p < 0.0001) compared to patients with visceral AS. The median overall survival in the entire cohort was 21.6 months. A total of 10 drug-related serious adverse effects were reported in 5 patients, including a fatal hepatic failure. Although our study did not meet its primary endpoint, the median PFS of 11.6 months in patients with superficial AS appears to be promising. Taking recent reports into consideration, future studies should evaluate the safety and efficacy of VEGFR and immune checkpoint inhibitors with or without paclitaxel in a randomized, multiarm setting.

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“… 21 , 22 , 23 The results of different treatments vary widely and are affected by many factors, such as tumor location, tumor size, resectability, and tumor type. 13 , 24 , 25 According to previous studies, 26 , 27 radical surgery remains the standard therapy for localized AS among different therapeutic approaches. It is still considered to be the most valid method to improve the 5‐year survival rate of AS.…”

Section: Discussionmentioning

confidence: 99%

New nomograms to predict overall and cancer‐specific survival of angiosarcoma

Liu

Pan

et al. 2021

Cancer Medicine

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Objective This study was designed to establish and validate promising and reliable nomograms for predicting the survival of angiosarcoma (AS) patients. Methods The Surveillance, Epidemiology, and End Results database was queried to collect the clinical information of 785 AS patients between 2004 and 2015. Data were split into a training cohort (n = 549) and a validation cohort (n = 236) without any preference. Univariate Cox and multivariate Cox regression analyses were performed to analyze the clinical parameters. Independent prognostic factors were then identified. Two nomograms were constructed to predict overall survival (OS) and cancer‐specific survival (CSS) at 3 and 5 years. Finally, the models were evaluated using concordance indices (C‐indices), calibration plots, and decision curve analysis (DCA). Results Based on the inclusion and exclusion criteria, 785 individuals were included in this analysis. Univariate and multivariate Cox regression analyses revealed that age, tumor size, and stage were prognostic factors independently associated with the OS of AS. Tumor site, tumor size, and stage were associated with the CSS of AS. Based on the statistical results and clinical significance of variables, nomograms were built. The nomograms for OS and CSS had C‐indices of 0.666 and 0.654, respectively. The calibration curves showed good agreement between the predictive values and the actual values. DCA also indicated that the nomograms were clinically useful. Conclusion We established nomograms with good predictive ability that could provide clinicians with better predictions about the clinical outcomes of AS patients.

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Optimal Clinical Management and the Molecular Biology of Angiosarcomas

Cited by 16 publications

References 132 publications

Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma

Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma

Treatment of Angiosarcoma with Pazopanib and Paclitaxel: Results of the EVA (Evaluation of Votrient® in Angiosarcoma) Phase II Trial of the German Interdisciplinary Sarcoma Group (GISG-06)

New nomograms to predict overall and cancer‐specific survival of angiosarcoma

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