Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans. EXPERIMENTAL DESIGN: ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis. RESULTS: Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype. CONCLUSIONS: Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950-9. ©2016 AACR.

Quality of life and health status among prostate cancer survivors and noncancer population controls.

OBJECTIVE: To examine whether quality of life (QOL), health status, and the relationships between them varied by having a prostate cancer history. This study helps to inform the interface between aging-related health decline and the survival state among older men with prostate cancer, which is an important yet understudied public health issue. METHODS: Hierarchical linear models were used to analyze the cross-sectional data from the nationally representative population-based Medical Expenditure Panel Survey. Using propensity score matching, survivors (respondents with prostate cancer history) and controls (respondents without a history of any cancer) (N = 193 pairs) were matched based on 7 sociodemographic and health-related factors. QOL was measured using the mental and physical component scores of the SF-12 (SF-36.org). Health status included comorbidities, activities of daily living (ADL), instrumental ADL, and depressed mood. RESULTS: In bivariate analyses, survivors reported worse physical (42.72 vs 45.45 respectively; P = .0040) and mental QOL (51.59 vs 53.73 respectively; P = .0295) and more comorbidities (3.25 vs 2.78 respectively; P = .0139) than controls. In multivariate analyses, for both survivors and controls, better physical QOL was associated with fewer comorbidities (P <.0001), no need help with ADL (P = .0011) and IADL (P = .0162), and less depressed mood (P <.0001); better mental QOL was associated with no need help with IADL (P = .0005) and less depressed mood (P <.0001). CONCLUSION: QOL of older men is affected by physical, functional, and psychological factors rather than prostate cancer history. Clinicians need to attend to aging-related health issues when providing care for prostate cancer survivors to improve QOL.