Dynamic changes of alkaline phosphatase are strongly associated with PSA-decline and predict best clinical benefit earlier than PSA-changes under therapy with abiraterone acetate in bone metastatic castration resistant prostate cancer.

BACKGROUND: Significant progress in treatment of metastatic castration resistant prostate cancer (mCRPC) has been made. Biomarkers to tailor therapy are scarce. To facilitate decision-making we evaluated dynamic changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) under therapy with Abiraterone. METHODS: Men with bone mCRPC (bmCRPC) on Abiraterone 12/2009-01/2014 were analyzed. Dynamic ALP-, LDH- and PSA-changes were analyzed as predictors of best clinical benefit and overall survival (OS) with logistic-regression, Cox-regression and Kaplan-Meier-analysis. RESULTS: Thirty-nine pre- and 45 post-chemotherapy patients with a median follow up of 14.0 months were analyzed. ALP-Bouncing can be observed very early during therapy with Abiraterone. ALP-Bouncing is defined as rapidly rising ALP-levels independent of baseline ALP during the first 2-4 weeks of Abiraterone-therapy with subsequent equally marked decline to pretreatment levels or better within 8 weeks of therapy, preceding potentially delayed PSA-decline. In univariate analysis failure of PSA-reduction ≥ 50% and failure of ALP-Bouncing were the strongest predictors of progressive disease (p = 0.003 and 0.021). Rising ALP at 12 weeks, no PSA-reduction ≥ 50% and no ALP-Bouncing were strongest predictors of poor OS, (all p < 0.001). Kaplan-Meier-analysis showed worse OS for rising ALP at 12 weeks, no PSA-reduction ≥ 50% and no ALP-Bouncing (p < 0.001). In subgroup-analysis of oligosymptomatic patients all parameters remained significant predictors of poor OS, with no PSA-reduction ≥ 50% and rising ALP at 12 weeks being the strongest (p < 0.001). In multivariate analysis PSA-reduction ≥ 50% remained an independent predictor of OS for the whole cohort and for the oligosymptomatic subgroup (both p = 0.014). No patient with ALP-Bouncing had PD for best clinical benefit. Patients with rising ALP at 12 weeks had no further benefit of Abiraterone. CONCLUSIONS: Dynamic changes of ALP, LDH and PSA during Abiraterone-therapy are associated with best clinical benefit and OS in bmCRPC. ALP-Bouncing occurring earlier than PSA-changes as well as prior to equivocal imaging results and rising ALP at 12 weeks under Abiraterone may help to decide whether to discontinue Abiraterone. An external validation of these findings on a prospective cohort is planned.

Left ventricular dilation and functional impairment assessed by gated SPECT are indicators of cardiac allograft vasculopathy in heart transplant recipients.

BACKGROUND: Coronary angiography (CA) is the standard method for diagnosis of cardiac allograft vasculopathy (CAV). Little is known about the value of measuring left ventricular function over time, which can be derived from gated myocardial perfusion single-photon emission computed tomography (SPECT). We evaluated the potential of measuring myocardial perfusion and left ventricular function with gated SPECT, as compared with CA, to detect CAV in the follow-up of heart transplantation. METHODS: One hundred sixty-one heart transplant recipients (137 men, 24 women, age 50.7 ± 12.2 years) were followed-up for 4.2 ± 2.0 years by annual routine gated perfusion SPECT and consecutive CA. Myocardial perfusion was quantified by summed stress, rest and difference scores (SSS, SRS and SDS, respectively). Left ventricular function (ESV, EDV and LVEF) was derived from gated SPECT. Both were compared with angiographically defined stages of CAV. RESULTS: ESV/EDV derived from gated SPECT increased from 61 ± 25 ml/169 ± 39 ml in patients with no CAV over 74 ± 38 ml/188 ± 55 ml in patients with moderate CAV to 153 ± 75 ml/278 ± 86 ml in patients with severe CAV (p < 0.01 and p < 0.001), whereas LVEF decreased from 64 ± 10% over 62 ± 11% to 47 ± 13% in patients with severe CAV (p < 0.001). Perfusion quantified by SRS and SSS increased from 1.2 ± 1.5/1.9 ± 2.3 over 1.9 ± 1.4/2.8 ± 2.0 to 6.5 ± 5.1/7.7 ± 5.8 in patients with severe CAV (p < 0.01). Overall, for the prediction of severe CAV, accuracy was found to be higher for gated SPECT functional analysis as compared with perfusion analysis. CONCLUSIONS: Impaired left ventricular function, as assessed by gated SPECT, correlated significantly with CAV. Thus, for this purpose, gated SPECT offers higher sensitivity than analysis of perfusion while having a comparable specificity.