Clinical factors that affect the establishment of soft tissue sarcoma patient-derived orthotopic xenografts: A University of California, Los Angeles, sarcoma program prospective clinical trial abstract

Tara A. Russell, Mark A. Eckardt, Takashi Murakami, Irmina A. Elliott, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, Robert M. Hoffman, Fritz C. Eilber

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Purpose Given the diverse and aggressive nature of soft tissue sarcomas (STSs), a need exists for more-precise therapy. Patient-derived orthotopic xenografts (PDOXs) provide a unique platform for personalized treatment. Thus, identification of patient and treatment factors that predict PDOX establishment is important. This study assessed the feasibility of incorporating PDOXs into the clinical setting and identifying factors associated with PDOX establishment. Patients and MethodsFromMay2015 toMay2016, 107 patients with biopsy-proven or potential STSwereenrolled.Tumorsampleswereobtained intraoperatively andorthotopically implanted into nude mice in the corresponding anatomic location. PDOXs were considered established after engraftment and serial passage. Factors associated with establishment were analyzed by logistic regression and time to establishment by time-to-event analysis. Results Only high-grade tumors established (32 of 72 [44.4%]). The establishment rate (ER) varied by neoadjuvant therapy and treatment response, with the highest ER among untreated high-grade tumors (26 of 42 [61.9%]). Tumors exposed to radiation preoperatively did not establish (zero of 11 [0%]), and tumors exposed to neoadjuvant chemotherapy had a lower ER (31.9%) than untreated tumors. Only STSs with minimal pathologic response to neoadjuvant treatment (≤ 30%) established a PDOX (six of 18 [33.3%]). Median establishment time was 54 days, which varied by neoadjuvant therapy but was not statistically significant (P = .180). Conclusion To our knowledge, in the largest STS PDOX study to date, we demonstrate a 62% ER among untreated high-grade tumors with a median establishment time of 54 days. Neoadjuvant therapy, particularly radiation, and pathologic response to treatment were associated with a reduced rate of PDOX establishment.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalJCO Precision Oncology
Volume2017
Issue number1
DOIs
Publication statusPublished - 2017
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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