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 METHODS: 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. 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.
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 METHODS: 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. 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.
Authors: David J Monsma; David M Cherba; Patrick J Richardson; Sean Vance; Sanjeet Rangarajan; Dawna Dylewski; Emily Eugster; Stephanie B Scott; Nicole L Beuschel; Paula J Davidson; Richard Axtell; Deanna Mitchell; Eric P Lester; Joseph J Junewick; Craig P Webb; Noel R Monks Journal: Pediatr Blood Cancer Date: 2014-03-31 Impact factor: 3.167
Authors: Kathleen B Smith; Linh M Tran; Brenna M Tam; Elizabeth M Shurell; Yunfeng Li; Daniel Braas; William D Tap; Heather R Christofk; Sarah M Dry; Fritz C Eilber; Hong Wu Journal: Am J Pathol Date: 2013-02-12 Impact factor: 4.307
Authors: Timothy R Donahue; Michael W Kattan; Scott D Nelson; William D Tap; Frederick R Eilber; Fritz C Eilber Journal: Cancer Date: 2010-08-15 Impact factor: 6.860
Authors: Fritz C Eilber; Murray F Brennan; Frederick R Eilber; Sarah M Dry; Samuel Singer; Michael W Kattan Journal: Cancer Date: 2004-11-15 Impact factor: 6.860
Authors: Justin Stebbing; Keren Paz; Gary K Schwartz; Leonard H Wexler; Robert Maki; Raphael E Pollock; Ronnie Morris; Richard Cohen; Arjun Shankar; Glen Blackman; Victoria Harding; David Vasquez; Jonathan Krell; Stergios Zacharoulis; Daniel Ciznadija; Amanda Katz; David Sidransky Journal: Cancer Date: 2014-04-04 Impact factor: 6.860
Authors: Zhenyang Liu; Michael Ho-Young Ahn; Tomohiro Kurokawa; Amy Ly; Gong Zhang; Fuyou Wang; Teppei Yamada; Ananthan Sadagopan; Jane Cheng; Cristina R Ferrone; Andrew S Liss; Kim C Honselmann; Gregory R Wojtkiewicz; Soldano Ferrone; Xinhui Wang Journal: J Transl Med Date: 2020-06-24 Impact factor: 5.531