Vol.:(0123456789) 1 3 Cancer Chemotherapy and Pharmacology https://doi.org/10.1007/s00280-020-04081-5 ORIGINAL ARTICLE In vitro drug sensitivity (IDS) of patient‑derived primary osteosarcoma cells as an early predictor of the clinical outcomes of osteosarcoma patients Jeerawan Klangjorhor 1  · Areerak Phanphaisarn 2  · Pimpisa Teeyakasem 1  · Parunya Chaiyawat 1  · Phichayut Phinyo 3  · Jongkolnee Settakorn 1,4  · Nipon Theera‑Umpon 5,6  · Dumnoensun Pruksakorn 1,2,5 Received: 5 February 2020 / Accepted: 13 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Purpose Early prediction of clinical response to conventional chemotherapy is a signifcant factor in determining an overall treatment strategy for osteosarcoma. Methods Cells were extracted from treatment-naïve biopsies from 16 osteosarcoma patients who received a doxorubicin and cisplatin-based neoadjuvant chemotherapy regimen and their sensitivities to doxorubicin and cisplatin were measured as IC50 values. Associations of in vitro drug sensitivity (IDS) levels and clinical outcomes were examined. Results Primary osteosarcoma cells responded to doxorubicin and cisplatin with IC50 values of 0.088 ± 0.032 µM and 16.7 ± 8.5 µM, respectively. The patients with a non-metastatic phenotype and surviving patients showed signifcantly lower IC50 values for both drugs. ROC analysis defned the optimal IC50 cut-of values for doxorubicin (IDS dox ) and cisplatin (IDS cpt ) as 0.05 µM (AUC 0.82) and 14 µM (AUC 0.87), respectively. Survival analysis found signifcantly longer disease- free survival (DFS, n = 14) and overall survival (OS, n = 16) times in the patients with low IDS dox (p = 0.0064 for DFS and p = 0.0102 for OS) and low IDS cpt (p = 0.0204 for DFS and p = 0.0021 for OS). Interestingly, when the patients with low IDS cpt and those with low IDS dox were combined (Group 1), signifcant associations with prolonged DFS (p = 0.0042, C-statistic 0.78) and OS (p = 0.0010, C-statistic 0.79) were found. In this cohort, histological response to neoadjuvant chemotherapy could predict only OS. Conclusions This study indicates that IDS analysis could potentially be a practical, rapid, and reliable technique for predict- ing clinical outcomes. It could also be used to identify patients for whom conventional chemotherapy is most appropriate and, in the future, help advance personalized therapy. Keywords IC50 · Chemotherapy · Predictive testing · Precision medicine · Osteosarcoma · Survival rate Abbreviations IDS In vitro drug sensitivity MTT Microculture tetrazolium assay DFS Disease-free survival OS Overall survival Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00280-020-04081-5) contains supplementary material, which is available to authorized users. * Dumnoensun Pruksakorn dumnoensun.p@cmu.ac.th 1 Musculoskeletal Science and Translational Research Center, Chiang Mai University, Chiang Mai 50200, Thailand 2 Department of Orthopedics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand 3 Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Ching Mai University, Chiang Mai, Thailand 4 Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand 5 Biomedical Engineering Institute, Chiang Mai University, Chiang Mai, Thailand 6 Department of Electrical Engineering, Faculty of Engineering, Chiang Mai University, Chiang Mai, Thailand