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Human cancers nearly ubiquitously harbor epigenetic alterations. While such alterations in epigenetic marks, including DNA methylation, are potentially heritable, they can also be dynamically altered. Given this potential for plasticity, the degree to which epigenetic changes can be subject to selection and act as drivers of neoplasia has been questioned. Here, we carried out genome-scale analyses of DNA methylation alterations in lethal metastatic prostate cancer and created DNA methylation “cityscape” plots to visualize these complex data. We show that somatic DNA methylation alterations, despite showing marked inter-individual heterogeneity among men with lethal metastatic prostate cancer, were maintained across all metastases within the same individual. The overall extent of maintenance in DNA methylation changes was comparable to that of genetic copy number alterations. Regions that were frequently hypermethylated across individuals were markedly enriched for cancer and development/differentiation related genes. Additionally, regions exhibiting high consistency of hypermethylation across metastases within individuals, even if variably hypermethylated across individuals, showed enrichment of cancer-related genes. Interestingly, whereas some regions showed intra-individual metastatic tumor heterogeneity in promoter methylation, such methylation alterations were generally not correlated with gene expression. This was despite a general tendency for promoter methylation patterns to be strongly correlated with gene expression, particularly at regions that were variably methylated across individuals. These findings suggest that DNA methylation alterations have the potential for producing selectable driver events in carcinogenesis and disease progression and highlight the possibility of targeting such epigenome alterations for development of longitudinal markers and therapeutic strategies.

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Objective To determine whether the pretreatment neutrophil-to-lymphocyte ratio (NLR), a measure of systemic inflammatory response, is associated with overall survival (OS) in men receiving chemotherapy with docetaxel for metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Records from 238 consecutive patients who were treated with first-line docetaxel-containing chemotherapy for mCRPC at a single high-volume centre from 1998 to 2010 (and who had adequate information to enable calculation of NLR) were reviewed. Univariable and multivariable Cox regression models were used to predict OS after chemotherapy initiation. Results In univariable analyses, the NLR as a discrete variable (optimal threshold 3.0) was significantly associated with OS (P = 0.001). In multivariable analyses, a lower NLR (≤3.0) was associated with lower risk of all-cause mortality (P = 0.002). In Kaplan-Meier analysis, the median OS was higher (18.3 vs 14.4 months) in patients that did not have an elevated NLR than in those with an elevated NLR (log-rank; P < 0.001). Conclusions Men who were treated with first-line docetaxel for mCRPC who had a low pretreatment NLR (≤3.0) had significantly longer OS. NLR may be a potentially useful clinical marker of systemic inflammatory response in predicting OS in men with mCRPC who receive docetaxel and may be helpful to stratify patients for clinical trials. These findings derived from a retrospective analysis need to be validated in larger populations in prospective studies, and in the context of different therapies.

not alter the adverse effects of antiangiogenic therapy.• Local tumour control 15 months after SRS was 98% (95% confidence interval 89-99%). The median pain score before SRS was 5 (range 1-8) and was lowered to 0 (range 0-2, P < 0.01) after SRS. There were no treatment-related deaths or late complications after SRS.• Overall survival was 17.4 months in patients with spinal lesions and 11.1 month in patients with cerebral lesions ( P = 0.038). CONCLUSIONS• Simultaneous systemic anti-angiogenic therapy and SRS for selected patients with renal cell carcinoma who have spinal and cerebral metastases is safe and effective.• Single-fraction delivery allows for efficacious integration of focal radiation treatment into oncological treatment concepts without additional toxicity.• Further studies are needed to determine the limits of SRS for renal cell carcinoma metastases outside the brain and spine. KEYWORDSrenal cell cancer, cyberknife, sunitinib, sorafenib, stereotactic, robotic surgery, spinal tumours, cerebral metastasis What's known on the subject? and What does the study add? To date radiation therapy has had no oncological implication in renal cell carcinoma. Its use was limited to palliation in painful bone lesions. Radiation therapy was considered ineffective as renal cell cancer is resistant to the commonly used doses of radiotherapy. Side effects in combination with systemic therapy were not known, but heavy skin toxicities were expected. Only a few cases of combined radiation with systemic therapy were published. This is the only series where consecutive patients have been treated simultaneously with sunitnib and hypo-fractionated high-dose radiotherapy. Side effects were similar to those expected with systemic therapy or radiation therapy alone. Oncological results are extremely encouraging.Study Type -Therapy (case series) Level of Evidence 4 OBJECTIVE• To analyse the safety and efficacy of simultaneous standard anti-angiogenic therapy and stereotactic radiosurgery (SRS) in patients with spinal and cerebral metastases from renal cell carcinoma. PATIENTS AND METHODS• In all, 106 patients with spinal ( n = 55) or cerebral ( n = 51) metastatic lesions and an Eastern Cooperative Oncology Group status of 0 or 1 were treated with sorafenib or sunitinib and simultaneous SRS.• The primary endpoint was local control.• Secondary endpoints were toxicity and overall survival.

Background: Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo-and radiotherapy in vitro.

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Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.