Author:
Golan Shay,Bar Vered,Salpeter Seth J.,Neev Guy,Creiderman German,Kedar Daniel,Aharon Sara,Turovsky Lubov,Zundelevich Adi,Shahar Hamutal,Shapira Hagit,Mallel Giuseppe,Stossel Erez,Gavert Nancy,Straussman Ravid,Dotan Zohar,Berger Raanan,Stossel Chani,Golan Talia,Halperin Sharon,Leibovici Dan,Breuer Shani,Rottenberg Yakir,Applebaum Liat,Hubert Ayala,Nechushtan Hovav,Peretz Tamar,Zick Aviad,Chertin Boris,Koulikov Dmitry,Sonnenblick Amir,Rosenbaum Eli
Abstract
IntroductionEx 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.MethodsA 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).ResultsThe 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).ConclusionEVOC 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.