Maarten van der Doelen

Radium-223 therapy in advanced mCRPC patients

Biochemical and radiological response evaluation Changes inPSAandALPwere calculated frombaseline toweek 12 (after three injections), from baseline to end of therapy (approximately one month after the last injection) and as maximal percentage change at any time from baseline. Patients who had no baseline level, no follow-upmeasurements or received concomitant enzalutamide or abiraterone were excluded from biochemical response evaluation. More than 25 percent decline or increase from baseline of PSA, ALP and LD was considered to be clinically significant, according to Prostate Cancer Working Group 3 criteria. (10) Radiological evaluation was performed in patients who underwent evaluation of soft tissues within three months after completion or discontinuation of therapy. Statistical methods Survival time was defined as the time interval from date of first radium-223 injection to the date of death. Cox proportional hazards models were used to assess the prognostic significance of baseline variables in univariable and multivariable analysis. A multivariable Cox regression model was fitted by including variables in the model with a forward selection strategy based on Wald’s test at a significance level of 0.10 at every step. In case baseline variables were heavily skewed distributed or the proportional hazard assumption was not likely to hold, log transformation or categorization of variables was performed. To compare baseline characteristics between patients who completed and discontinued radium-223 therapy, the chi-square test or Fisher exact test was used. Statistical tests were performed two-sided, with p values <0.05 considered statistically significant. Survival curves for patients who completed therapy and patients who discontinued therapy were estimated by the Kaplan-Meier estimator. The Mantel-Cox log rank test was used to compare the survival distributions. Statistical analyses were performed using SPSS 22.0 (IBM®, Armonk, NY, USA). Figures were created with SPSS and Graphpad Prism 5.03 (GraphPad Software, Inc., La Jolla, CA, USA). Ethics This study was approved by the medical ethics review committee. The principles of the Helsinki Declaration were followed.

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