CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer.

Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included. On a single axial CT section obtained at the mid-L5 level, the mean CT attenuation of the trabecular bone of the L5 vertebral body (L5HU) was measured. The height-normalized psoas cross-sectional area (PsoasL4-5) was measured on a single CT section obtained at the L4-5 vertebral interface. Multivariable Cox proportional hazards models were used to assess effects on noncancer death. By using parameter estimates from an adjusted model, a prognostic index for prediction of noncancer death was generated and compared with age-adjusted Charlson Comorbidity Index (CCI) by using the Harrell c statistic. Results Six hundred fifty-three men met the inclusion criteria. Prostate cancer risk grouping, androgen deprivation, race, age-adjusted CCI, L5HU, and PsoasL4-5 were included in a multivariable model. Age-adjusted CCI (hazard ratio [HR] = 1.36, P < .001), L5HU (HR = 2.88 for L5HU < 105 HU, HR = 1.42 for 105 HU ≤ L5HU ≤ 150 HU, P < .001), PsoasL4-5 (HR = 1.95 for PsoasL4-5 < 7.5 cm2/m2, P = .003), and race (HR = 1.68 for African American race, HR = 1.77 for other nonwhite race, P = .019) were independent predictors of noncancer death. The prognostic index yielded a c value of 0.747 for the prediction of noncancer death versus 0.718 for age-adjusted CCI alone. Conclusion L5HU and PsoasL4-5, which are surrogates for bone mineral density and muscle mass, respectively, were independent predictors of noncancer death. The prognostic index that incorporated these measures with the CCI was associated with improved accuracy for prediction of noncancer death. © RSNA, 2016 Online supplemental material is available for this article.

Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed. In this review, we detail the mechanisms from which genomic instability arises and can lead to cancer, as well as treatments and measures that prevent genomic instability or take advantage of the cellular defects caused by genomic instability. In particular, we identify and discuss five priority targets against genomic instability: (1) prevention of DNA damage; (2) enhancement of DNA repair; (3) targeting deficient DNA repair; (4) impairing centrosome clustering; and, (5) inhibition of telomerase activity. Moreover, we highlight vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates as priority approaches against genomic instability. The prioritized target sites and approaches were cross validated to identify potential synergistic effects on a number of important areas of cancer biology.

PSA response to neoadjuvant androgen deprivation is an independent prognostic marker and may identify patients who benefit from treatment escalation.

PURPOSE: To determine whether prostate-specific antigen (PSA) measurement after initiation of androgen deprivation therapy (ADT) but prior to the start of radiotherapy (RT) pPSA is an independent predictor of biochemical relapse-free survival (bRFS). We also sought to determine the effect, if any, of factors affecting bRFS for patients who did not achieve pPSA<0.5 ng/mL. METHODS AND MATERIALS: A total of 105 patients with National Comprehensive Cancer Network intermediate- or high-risk prostate cancer treated with neoadjuvant ADT (median = 3.9 mo) and external beam RT had pPSA data available and met the inclusion criteria. Pretreatment and treatment characteristics were included in a Cox proportional hazards model to determine effect on bRFS. RESULTS: Median follow-up was 5.4 years. On multivariable analysis, pPSA≥0.5 ng/mL was associated with worsened bRFS (hazard ratio [HR] = 2.7, P = 0.013). For the subgroup of patients with at most 1 high-risk factor, pPSA remained a statistically significant prognostic factor. For patients within this subgroup who had pPSA≥0.5 ng/mL, the addition of pelvic RT was associated with a trend toward improved outcome (HR = 0.609, P = 0.083). CONCLUSION: For patients with intermediate- or high-risk prostate cancer receiving neoadjuvant ADT, achieving pPSA<0.5 ng/mL was associated with improved rates of bRFS. Additionally, pPSA measurement may identify patients who may be able to benefit from escalated treatment such as pelvic RT.