TY - JOUR
T1 - A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy
AU - Golan, Shay
AU - Bar, Vered
AU - Salpeter, Seth J.
AU - Neev, Guy
AU - Creiderman, German
AU - Kedar, Daniel
AU - Aharon, Sara
AU - Turovsky, Lubov
AU - Zundelevich, Adi
AU - Shahar, Hamutal
AU - Shapira, Hagit
AU - Mallel, Giuseppe
AU - Stossel, Erez
AU - Gavert, Nancy
AU - Straussman, Ravid
AU - Dotan, Zohar
AU - Berger, Raanan
AU - Stossel, Chani
AU - Golan, Talia
AU - Halperin, Sharon
AU - Leibovici, Dan
AU - Breuer, Shani
AU - Rottenberg, Yakir
AU - Applebaum, Liat
AU - Hubert, Ayala
AU - Nechushtan, Hovav
AU - Peretz, Tamar
AU - Zick, Aviad
AU - Chertin, Boris
AU - Koulikov, Dmitry
AU - Sonnenblick, Amir
AU - Rosenbaum, Eli
PY - 2023/9/28
Y1 - 2023/9/28
N2 - Introduction: Ex vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy. Methods: A multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 μM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients’ clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST). Results: The cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4–0.97) and a sensitivity of 96% (24/25, 95% CI 0.80–0.99). Conclusion: EVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors.
AB - Introduction: Ex vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy. Methods: A multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 μM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients’ clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST). Results: The cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4–0.97) and a sensitivity of 96% (24/25, 95% CI 0.80–0.99). Conclusion: EVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors.
UR - http://www.scopus.com/inward/record.url?scp=85174158002&partnerID=8YFLogxK
U2 - 10.3389/fmed.2023.1221484
DO - 10.3389/fmed.2023.1221484
M3 - Article
AN - SCOPUS:85174158002
SN - 2296-858X
VL - 10
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 1221484
ER -