Factors that influence response classifications in chemotherapy treated patient-derived xenografts (PDX).

Autor:	Malcolm JE; The Jackson Laboratory, Bar Harbor, ME, United States of America.; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, United States of America., Stearns TM; The Jackson Laboratory, Bar Harbor, ME, United States of America., Airhart SD; The Jackson Laboratory, Bar Harbor, ME, United States of America., Graber JH; The Jackson Laboratory, Bar Harbor, ME, United States of America.; The MDI Biological Laboratory, Bar Harbor, ME, United States of America., Bult CJ; The Jackson Laboratory, Bar Harbor, ME, United States of America.
Jazyk:	angličtina
Zdroj:	PeerJ [PeerJ] 2019 Mar 28; Vol. 7, pp. e6586. Date of Electronic Publication: 2019 Mar 28 (Print Publication: 2019).
DOI:	10.7717/peerj.6586
Abstrakt:	In this study, we investigated the impact of initial tumor volume, rate of tumor growth, cohort size, study duration, and data analysis method on chemotherapy treatment response classifications in patient-derived xenografts (PDXs). The analyses were conducted on cisplatin treatment response data for 70 PDX models representing ten cancer types with up to 28-day study duration and cohort sizes of 3-10 tumor-bearing mice. The results demonstrated that a 21-day dosing study using a cohort size of eight was necessary to reliably detect responsive models (i.e., tumor volume ratio of treated animals to control between 0.1 and 0.42)-independent of analysis method. A cohort of three tumor-bearing animals led to a reliable classification of models that were both highly responsive and highly nonresponsive to cisplatin (i.e., tumor volume ratio of treated animals to control animals less than 0.10). In our set of PDXs, we found that tumor growth rate in the control group impacted treatment response classification more than initial tumor volume. We repeated the study design factors using docetaxel treated PDXs with consistent results. Our results highlight the importance of defining endpoints for PDX dosing studies when deciding the size of cohorts to use in dosing studies and illustrate that response classifications for a study do not differ significantly across the commonly used analysis methods that are based on tumor volume changes in treatment versus control groups. Competing Interests: The authors declare there are no competing interests.
Databáze:	MEDLINE
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