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Diagnosis, Prognosis, and Treatment of Alveolar Soft-Part SarcomaA Review

Educational Objective:
To learn current approaches to the diagnosis and treatment of alveolar soft-part sarcomas.
1 Credit CME
Abstract

Importance  Alveolar soft-part sarcoma (ASPS) is a rare, translocation-driven sarcoma of the soft tissues. Alveolar soft-part sarcoma often affects young adults and is characterized by indolent behavior but early evidence of metastatic spread. After recognition of ASPS as a specific entity in 1952, retrospective data indicated prolonged survival in patients with metastases, despite inherent resistance to conventional doxorubicin-based chemotherapy. Tyrosine kinase inhibitors and immune checkpoint inhibitors have provided unexpected new treatment strategies for ASPS.

Observations  This review includes articles published between 1952 and March 1, 2018. With the introduction of new molecular diagnostic tools and therapies, the distinctive features of ASPS have become more evident. The identification and better understanding of molecular pathways activated by the characteristic t(X;17)(p11;q25) translocation and its correspondent chimeric ASPSCR1-transcription factor E3 (TFE3) fusion protein open new paths to drug development. The associations of TFE3 and facilitation of an immunosuppressive microenvironment provide a rationale for exploring treatments that affect the balance between T-effector cells and T-regulatory cells. Tyrosine kinase inhibitors, such as sunitinib, cediranib, and pazopanib, show activity with either tumor responses or disease stabilization in more than 50% of the cases. Given the association of new agents with patient outcomes, it is too early to say whether metastatic ASPS should still be considered incurable in all patients.

Conclusions and Relevance  The biologic outcomes of the canonical genomic event in ASPS remain under investigation; a better understanding of the tumor microenvironment and the multiple pathways activated in this sarcoma, including unusual bioenergetics, MET signaling, and angiogenesis, should lead to more rational therapy. Basket trials and related prospective studies focusing on the intersection of specific signaling pathways and diseases with unique genomic features, such as ASPS, will provide an understanding of new options for care.

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Article Information

Accepted for Publication: July 5, 2018.

Corresponding Author: Luca Paoluzzi, MD, Department of Medicine, New York University Langone Medical Center, 160 E 34th St, 10th Flr, Room 1011, New York, NY 10016 (luca.paoluzzi@nyumc.org).

Published Online: October 18, 2018. doi:10.1001/jamaoncol.2018.4490

Author Contributions: Drs Paoluzzi and Maki had full access to all the data in the study and take responsibility of the integrity of the data and the accuracy of the data analysis.

Concept and design: Both authors.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Both authors.

Critical revision of the manuscript for important intellectual content: Both authors.

Administrative, technical, or material support: Paoluzzi.

Conflict of Interest Disclosures: Dr Maki is a board member and member of the medical oncology examination committee for American Board of Internal Medicine; receives consultant fees from Aadi Bioscience, Karyopharm Therapeutics, Deciphera data and safety monitoring board, Arcus, Bayer, Eisai, Immune Design, Janssen, Pharma Mar, Presage, Tracon, and Sarcoma Alliance for Research Through Collaboration (SARC); and research support to New York University from Immune Design, Immunocore, Lilly, Presage, Tracon, SARC, Regeneron, and Genentech. No other conflicts were reported.

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