Deep Functional and Molecular Characterization of a High-Risk Undifferentiated Pleomorphic Sarcoma

Noah E Berlow; Catherine S Grasso; Michael J Quist; Mingshan Cheng; Regina Gandour-Edwards; Brian S Hernandez; Joel E Michalek; Christopher Ryan; Paul Spellman; Ranadip Pal; Lynn S Million; Mark Renneker; Charles Keller

doi:10.1155/2020/6312480

Deep Functional and Molecular Characterization of a High-Risk Undifferentiated Pleomorphic Sarcoma

Sarcoma. 2020 May 4:2020:6312480. doi: 10.1155/2020/6312480. eCollection 2020.

Authors

Noah E Berlow^{1

2

3}, Catherine S Grasso³, Michael J Quist³, Mingshan Cheng⁴, Regina Gandour-Edwards⁵, Brian S Hernandez⁶, Joel E Michalek⁶, Christopher Ryan⁷, Paul Spellman⁷, Ranadip Pal², Lynn S Million⁸, Mark Renneker^{9

10}, Charles Keller^{1

2}

Affiliations

¹ Children's Cancer Therapy Development Institute, Beaverton, OR 97005, USA.
² Electrical and Computer Engineering, Texas Tech University, Lubbock, TX 79409, USA.
³ Division of Hematology-Oncology, University of California, Los Angeles, CA 90095, USA.
⁴ The Jackson Laboratory, Bar Harbor, ME 04609, USA.
⁵ Department of Pathology & Laboratory Medicine, UC Davis Health System, Sacramento, CA 95817, USA.
⁶ Department of Epidemiology and Biostatistics, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA.
⁷ School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA.
⁸ Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.
⁹ Patient-Directed Consultations, San Francisco, CA 94116, USA.
¹⁰ Department of Family Medicine, University of California San Francisco, San Francisco, CA 94143, USA.

Abstract

Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic, ex vivo live cell chemosensitivity testing, a patient-derived xenograft model, and immunoscoring. Her therapeutic choices were also diverse, including neoadjuvant chemotherapy, radiation therapy, and surgeries. Adjuvant and recurrence strategies included off-label and natural medicines, several immunotherapies, and N-of-1 approaches. Identified treatment options, especially those validated during the in vivo study, were not introduced into the course of clinical treatment but did provide plausible treatment regimens based on FDA-approved clinical agents.