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

  • Tara A. Russell
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Mark A. Eckardt
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Takashi Murakami
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Irmina A. Elliott
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Kei Kawaguchi
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Tasuku Kiyuna
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Kentaro Igarashi
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Yungfeng Li
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Joseph G. Crompton
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Danielle S. Graham
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Sarah M. Dry
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Nicholas Bernthal
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Jane Yanagawa
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Anusha Kalbasi
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Noah Federman
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Bartosz Chmielowski
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Arun S. Singh
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Robert M. Hoffman
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...
  • Fritz C. Eilber
    Tara A. Russell, Irmina A. Elliott, Yungfeng Li, Joseph G. Crompton, Danielle S. Graham, Sarah M. Dry, Nicholas Bernthal, Jane Yanagawa, Anusha Kalbasi, Noah Federman, Bartosz Chmielowski, Arun S. Singh, and Fritz C. Eilber, University of California, Los Angeles; Tara A. Russell, Veterans Affairs Los Angeles Health Services Research & Development Center of Innovation, Los Angeles, CA; Mark A. Eckardt, Yale School of Medicine, New Haven, CT; Takashi Murakami, Kei Kawaguchi, Tasuku Kiyuna, Kentaro Igarashi...

説明

<jats:sec><jats:title>Purpose</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> From May 2015 to May 2016, 107 patients with biopsy-proven or potential STS were enrolled. Tumor samples were obtained intraoperatively and orthotopically 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. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> 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). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> 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. </jats:p></jats:sec>

収録刊行物

  • JCO Precision Oncology

    JCO Precision Oncology (1), 1-13, 2017-11

    American Society of Clinical Oncology (ASCO)

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