Yuan Cheng1, Shu-Kui Qin2, Jin Li3, Guang-Hai Dai4, Bai-Yong Shen5, Jie-Er Ying6, Yi Ba7, Han Liang7, Xin-Bo Wang8, Ye Xu9, Lin Zhou10, Ke-Feng Ding11, Yan-Ru Qin12, Shu-Jun Yang13, Wen-Xian Guan14, Hui Zheng15, Qian Wang15, Hang Song15, Yan-Ping Zhu15. 1. Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. 2. Bayi Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. qinsk@csco.org.cn. 3. Shanghai East Hospital Affiliated to Tongji University, Shanghai, China. fudanlijin@163.com. 4. Chinese PLA General Hospital, Beijing, China. 5. Shanghai Ruijin Hospital, Shanghai, China. 6. Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China. 7. Tianjin Cancer Hospital, Tianjin, China. 8. Eastern Theater General Hospital of Chinese PLA, Nanjing, Jiangsu, China. 9. Shanghai Cancer Hospital, Shanghai, China. 10. 302 Military Hospital of Chinese PLA, Beijing, China. 11. The Second Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China. 12. The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, China. 13. Henan Cancer Hospital, Zhengzhou, Henan, China. 14. Drum Tower Hospital Affiliated to Nanjing University School of Medicine, Nanjing, Jiangsu, China. 15. Nanjing Personal Oncology Biological Technology Co. Ltd, Nanjing, Jiangsu, China.
Abstract
BACKGROUND: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers. METHODS: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis. RESULTS: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. CONCLUSION: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.
BACKGROUND: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers. METHODS: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis. RESULTS: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. CONCLUSION: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.
Authors: Harinarayanan Janakiraman; Yun Zhu; Scott A Becker; Cindy Wang; Ashley Cross; Emily Curl; David Lewin; Brenda J Hoffman; Graham W Warren; Elizabeth G Hill; Cynthia Timmers; Victoria J Findlay; Ernest R Camp Journal: Int J Cancer Date: 2020-02-03 Impact factor: 7.396
Authors: Berglind O Einarsdottir; Joakim Karlsson; Elin M V Söderberg; Mattias F Lindberg; Elisa Funck-Brentano; Henrik Jespersen; Siggeir F Brynjolfsson; Roger Olofsson Bagge; Louise Carstam; Martin Scobie; Tobias Koolmeister; Olof Wallner; Ulrika Stierner; Ulrika Warpman Berglund; Lars Ny; Lisa M Nilsson; Erik Larsson; Thomas Helleday; Jonas A Nilsson Journal: Cell Death Dis Date: 2018-07-24 Impact factor: 8.469