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Purpose: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI., Method: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival., Results: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001)., Conclusions: Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS., Trial Registration: EudraCtNo: 2005-004502-82., Competing Interests: The authors have read the journal’s policy and have the following competing interests: ANP has received a speaker fee and travel expenses from GE Healthcare. SJW has received travel expenses from IPSEN. GDS has received educational grants from Pfizer, Astra Zeneca, and Intuitive Surgical; consultancy fees from Merck, Pfizer, EUSA Pharma and CMR Surgical; travel expenses and speaker fees from Pfizer. AW received a single Scientific Advisory Board fee from Roche. TE has received research support from Pfizer and AstraZeneca, and honoraria from Pfizer. TE was employed by AstraZeneca during part of the study duration and is now employed by Roche, and holds stock in AstraZeneca and Roche. Pfizer provided the study drug Sunitinib and an educational grant for the translational endpoint analysis, reported separately. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. more...

Background: Evaluating tissue heterogeneity using non-invasive imaging could potentially improve prostate cancer assessment and treatment., Methods: 20 patients with intermediate/high-risk prostate cancer underwent diffusion kurtosis imaging, including calculation of apparent diffusion (Dapp) and kurtosis (Kapp), prior to radical prostatectomy. Whole-mount tissue composition was quantified into: cellularity, luminal space, and fibromuscular stroma. Peripheral zone tumors were subdivided according to Gleason score., Results: Peripheral zone tumors had increased cellularity (p<0.0001), decreased fibromuscular stroma (p<0.05) and decreased luminal space (p<0.0001). Gleason score ≥4+3 tumors had significantly increased cellularity and decreased fibromuscular stroma compared to Gleason score ≤3+4 (p<0.05). In tumors, there was a significant positive correlation between median Kapp and cellularity (ρ = 0.50; p<0.05), and a negative correlation with fibromuscular stroma (ρ = -0.45; p<0.05). In normal tissue, median Dapp had a significant positive correlation with luminal space (ρ = 0.65; p<0.05) and a negative correlation with cellularity (ρ = -0.49; p<0.05). Median Kapp and Dapp varied significantly between tumor and normal tissue (p<0.0001), but only median Kapp was significantly different between Gleason score ≥4+3 and ≤3+4 (p<0.05)., Conclusions: Peripheral zone tumors have increased cellular heterogeneity which is reflected in mean Kapp, while normal prostate has a more homogeneous luminal space and cellularity better represented by Dapp. more...

The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer. more...