Prediction of neo-adjuvant chemotherapy response in bladder cancer: the impact of clinical parameters and routine biomarkers.

PURPOSE: To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC). MATERIALS AND METHODS: The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factors affecting survival were estimated. RESULTS: The complete response rate after NAC was 44%. A higher number of chemotherapy cycles was associated with better response to neo-adjuvant chemotherapy. No response to neo-adjuvant chemotherapy and female gender was associated with decreased cancer-specific survival. The IHC stainings used failed to show an association with neo-adjuvant chemotherapy response and overall or cancer specific survival. CONCLUSIONS: Patients who do not respond to neo-adjuvant chemotherapy do significantly worse than responders. This study could not find clinical tools to distinguish responders from non-responders. Further studies preferably with larger cohorts addressing this issue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.

Effects of racing on equine fertility.

Racing and fertility are connected with each other in many ways. Stress and increased body temperature induced by racing may have negative effects on fertility, but on the other hand, high quality nutrition and management of racing horses may have positive effects. Fertility may also be genetically associated with racing performance. The analysed data consisted of Finnish mating records of Standardbreds (n=33,679) and Finnhorses (n=32,731), from 1991 to 2005, and the harness racing records of both mares and stallions. Fertility was measured by foaling outcome, and racing performance was measured by best time and number of races. We used racing results from the mating year and from the entire career, to study both short-term and long-term effects of racing on fertility. The analyses were conducted with a linear mixed model, where racing was fitted as a fixed factor. In a separate bivariate analysis we measured the genetic correlation of racing and fertility, applying a threshold model for the fertility trait. For mares, racing after the first mating or more than 10 times during the mating year diminished the foaling outcome. However, racing only before the first mating or 1-5 times during the mating year had positive effects on mare fertility. Stallion fertility did not suffer from racing during the mating year. The mares with the best career racing records had the highest foaling rates, but this was probably due to preferential treatment. The genetic correlation between best racing record and fertility was favourable but weak in the Finnhorse (-0.24±0.08), and negligible in the Standardbred (-0.15±0.11).

Effects of inbreeding and other genetic components on equine fertility.

The Finnish mating records of Standardbred trotters (SB; n = 33 679) and Finnhorses (FH; n = 32 731) were analysed to study the effect of the level of inbreeding on foaling rates and to estimate the heritability of foaling rate. A linear mixed model was assumed, with the outcome of the foaling (foal or no foal) as the trait of the study. A restricted maximum likelihood-based method was used to calculate the estimates of the variance components. Predictions of breeding values and estimates of fixed effects were also calculated. The average level of inbreeding was 9.9% in the SB and 3.6% in the FH. The average foaling rates were better in the SB (72.6%) than in the FH (66.3%), but within each breed intense inbreeding had a statistically significant negative effect on foaling rate (P < 0.05). Also, the mating type, the age and breeding type of the mare, and the age of the stallion had statistically significant effects on foaling rate (P < 0.001). The heritability of foaling rate was between 3.4% and 3.7% in SBs and between 5.5% and 9.8% in FHs, when the outcome of the foaling was considered to be a trait of the expected foal. With the same model, the estimates of maternal genetic effect were 4.7% for SBs and 3.2% for FHs, and the estimates of the permanent environmental effects of the stallion were between 1.3% and 1.7%. Avoiding matings with very high inbreeding coefficients would improve foaling rates. It would also be possible to devise a breeding program for better equine fertility, but because the heritability is low, improvement of environmental factors deserves special attention.