Neoadjuvant chemotherapy for primary cutaneous/soft tissue angiosarcoma: Determining tumor behavior prior to surgical resection

Oxenberg, Jacqueline; Salerno, Kilian E.; Attwood, Kristopher; Kane, John M.

doi:10.1002/jso.23891

Cited by 24 publications

(23 citation statements)

References 27 publications

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“…Radiotherapy is mostly used as adjuvant therapy or reserved for patients unsuitable for surgery or systemic treatment. However, more than 50% of localized AS patients will develop recurrence or metastasis within five years [19,20]. Other treatment modalities are crucial to improve survival of localized AS.…”

Section: Treatments For Localized Angiosarcomamentioning

confidence: 99%

Optimal Clinical Management and the Molecular Biology of Angiosarcomas

Chen

Burns

Jones

et al. 2020

Cancers

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Angiosarcomas comprise less than 3% of all soft tissue sarcomas but have a poor prognosis. Most angiosarcomas occur without obvious risk factors but secondary angiosarcoma could arise after radiotherapy or chronic lymphedema. Surgery remains the standard treatment for localized angiosarcoma but neoadjuvant systemic treatment may improve the curability. For advanced angiosarcoma, anthracyclines and taxanes are the main chemotherapy options. Anti-angiogenic agents have a substantial role but the failure of a randomized phase 3 trial of pazopanib with or without an anti-endoglin antibody brings a challenge to future trials in angiosarcomas. Immune checkpoint inhibitors as single agents or in combination with oncolytic virus may play an important role but the optimal duration remains to be investigated. We also report the current understanding of the molecular pathways involved in angiosarcoma pathogenesis including MYC amplification, activation of angiogenic pathways and different molecular alterations that are associated with angiosarcomas of different aetiology. The success of the patient-partnered Angiosarcoma Project (ASCProject) has provided not only detailed insights into the molecular features of angiosarcomas of different origins but also offers a template for future fruitful collaborations between patients, physicians, and researchers. Lastly, we provide our perspective of future developments in optimizing the clinical management of angiosarcomas.

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Section: Treatments For Localized Angiosarcomamentioning

confidence: 99%

Optimal Clinical Management and the Molecular Biology of Angiosarcomas

Chen

Burns

Jones

et al. 2020

Cancers

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“…The standard of care for resectable localized disease is complete surgical resection. Despite this treatment, more than 50% of patients develop local (26–54%) or distant (>50%) recurrent disease [ 13 , 14 ] and only 60% of patients who initially present with localized disease survive for more than 5 years [ 15 ], meaning there is an urgent need to improve the treatment. Given this high-risk and poor prognosis of angiosarcoma, ESMO guidelines state that neoadjuvant radiation and chemotherapy may be considered [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant Systemic Treatment of Primary Angiosarcoma

Heinhuis

IJzerman

Graaf

et al. 2020

Cancers

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Angiosarcoma is an extremely rare and aggressive malignancy. Standard of care of localized tumors includes surgery ± radiation. Despite this multimodal treatment, >50% of the angiosarcoma patients develop local or distant recurrent disease. The role of neoadjuvant systemic therapy is still controversial and we therefore performed a systematic review of the literature to define the role of neoadjuvant systemic therapy based on available evidence. We focused on the effects of neoadjuvant systemic therapy on: 1. The success of surgical resection and 2. the long-term survival. All articles published before October 2019 on Ovid Medline, Ovid Embase, Cochrane library and Scopus were evaluated. Eighteen case reports and six retrospective cohort studies were included. There were no randomized controlled trials. This literature showed a beneficial role of neoadjuvant chemotherapy on downsizing of the tumor resulting in an improvement of the resection margins, especially in patients with cardiac or cutaneous angiosarcoma. However, no definitive conclusions on survival can be drawn based on the available literature lacking any prospective randomized studies in this setting. We advise that neoadjuvant chemotherapy should be considered, since this could lead to less mutilating resections and a higher rate of free resection margins. An international angiosarcoma registry could help to develop guidelines for this rare disease.

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“…Various additional drugs for systemic treatment have been investigated before. [2][3][4] Although the role of (neo)adjuvant chemotherapy remains controversial for localised disease, neoadjuvant chemotherapy is often administered for locally advanced angiosarcoma. 3 5-8 Several cytotoxic drugs, including anthracyclines, taxanes and gemcitabine, Strengths and limitations of this study ► The neoadjuvant setting provides the opportunity to evaluate the antitumor response of propranolol monotherapy without delaying the standard treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Open access have shown activity in angiosarcoma in the locally advanced and metastatic setting, with overall response rates varying from 17% to 89%. [2][3][4] However, for the treatment of resectable angiosarcoma, none of the previous studies shows a prolonged disease-free survival or overall survival. 3 5-10 Improved treatment in the neoadjuvant setting might reduce the local and distant recurrence rates by treating micrometastases at an early stage and by improving the resection margins, potentially leading to higher survival rates.…”

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confidence: 99%

PropAngio study protocol: a neoadjuvant trial on the efficacy of propranolol monotherapy in cutaneous angiosarcoma—a proof of principle study

et al. 2020

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IntroductionAngiosarcoma is a rare and aggressive malignancy with a high metastatic potential and recurrence rate. Despite optimal treatment with surgery, with or without radiation, the prognosis remains poor and, therefore, new treatment strategies are warranted. Recently, propranolol has effectively been repurposed for the treatment of infantile haemangioma. Propranolol is a β3-sparing antagonist of the β-adrenergic receptor. In infantile haemangioma, the β1, β2 and β3 receptors are highly expressed. Angiosarcoma has several similarities with haemangioma, including its high β-adrenergic receptor expression and the supposedly important role of vascular endothelial growth factor in malignant growth. As a result, propranolol has been administered small scale in individual angiosarcoma cases with promising results. The precise effect of propranolol, however, is not yet established.Methods and analysisThe goal of this neoadjuvant window of opportunity study is to prospectively evaluate the activity of propranolol monotherapy in patients with cutaneous angiosarcoma. The neoadjuvant setting provides a good opportunity to rapidly evaluate both the clinical response and histological response, without a significant delay in standard anticancer treatment. Fourteen patients with primary, recurrent or metastatic cutaneous angiosarcoma will be included. Propranolol will be administered orally in an escalating dose during 3–6 weeks, before the initiation of standard treatment. The primary endpoint is clinical response according to Response Evaluation Criteria in Solid Tumours, as measured on consecutive coloured photographs or CT/MRI. The histological response will be determined as secondary endpoint, comparing the difference in proliferation index before and after propranolol by measuring the change in immunohistochemistry staining of Ki-67. The study will be considered positive when at least three patients have a response to propranolol.Ethics and disseminationEthical approval was obtained from the Medical Ethical Committee of the Netherlands Cancer Institute. Independent of the outcome, results of this study will be shared and submitted for publication in an international peer-reviewed journal.Trial registration numberNL8118; registry through the Netherlands Trial Register.

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Neoadjuvant chemotherapy for primary cutaneous/soft tissue angiosarcoma: Determining tumor behavior prior to surgical resection

Abstract: NAC for primary AS was well tolerated. Although there was no statistically significant survival benefit, NAC helped define who would benefit from surgical resection.

Cited by 24 publications

References 27 publications

Optimal Clinical Management and the Molecular Biology of Angiosarcomas

Optimal Clinical Management and the Molecular Biology of Angiosarcomas

Neoadjuvant Systemic Treatment of Primary Angiosarcoma

PropAngio study protocol: a neoadjuvant trial on the efficacy of propranolol monotherapy in cutaneous angiosarcoma—a proof of principle study

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