Background: National guidelines endorse fluorine 18 ( 18 F) fluciclovine PET/CT for the detection of prostate cancer (PCa) in men with biochemically recurrent PCa. The comparative performance between fluciclovine and gallium 68 or 18 F prostate-specific membrane antigen (PSMA) PET/CT, a newer examination, is unclear.Purpose: To compare the detection of biochemical recurrence using fluciclovine versus PSMA-targeted radiotracers in patients with a prostate-specific antigen (PSA) level less than 2 ng/mL. Materials and Methods:With use of the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy, or PRISMA-DTA, guidelines, a systematic review of PubMed and EMBASE databases between 2012 and 2019 was performed. Studies of fluciclovine PET/CT or PSMA PET/CT in biochemical recurrence were identified. PSA levels, clinical data, and reference standards were obtained when available. A random-effects model was applied to pooled estimates and 95% confidence intervals (CIs) around the prevalence of a positive examination, stratified according to PSA tier.Results: Quantitative analysis included 482 patients (median age, 67 years; interquartile range, 67-67 years) in six fluciclovine studies and 3217 patients (median age, 68 years; interquartile range, 67-70 years) in 38 PSMA studies. Pooled detection rates for PSMA and fluciclovine were 45% (95% CI: 38%, 52%) and 37% (95% CI: 25%, 49%), respectively, for a PSA level less than 0.5 ng/mL (P = .46); 59% (95% CI: 52%, 66%) and 48% (95% CI: 34%, 61%) for a PSA level of 0.5-0.9 ng/mL (P = .19); and 80% (95% CI: 75%, 85%) and 62% (95% CI: 54%, 70%) for a PSA level of 1.0-1.9 ng/mL (P = .01). A reference standard was positive in 703 of 735 patients (96%) in the PSMA cohort and 247of 256 (97%) in the fluciclovine cohort. Conclusion:Patient-level detection rates for biochemically recurrent prostate cancer were greater for prostate-specific membrane antigen-targeted radiotracers than fluciclovine for prostate specific antigen levels of 1.0-1.9 ng/mL.

Emerging data suggest that primary dysfunction in the tumor microenvironment is crucial for carcinogenesis. These recent findings make a compelling case for targeting the milieu for cancer chemoprevention as well as therapy. The stroma is an integral part of its physiology, and functionally, one cannot totally dissociate the tumor surrounding from the tumor cells. A thorough understanding of the tumor and stroma will aid us in developing new treatment targets. In this review, we shed light at the key aspects of the carcinogenic process and how oxidative stress and inflammation contribute to this process. We dissect the connection between metastasis and oxidative stress and focus on the key players in the tumor microenvironment that leads to inflammation, oxidative stress and DNA damage. Moreover, we consider the role of inflammation in disease, specifically cancer and metastasis. Finally, we discuss the potential applications in prognosis and cancer treatment.

Aims Recently we found that mice bearing subcutaneous non-metastatic tumors exhibited elevated levels of two types of complex DNA damage, i.e., double-strand breaks and oxidatively-induced clustered DNA lesions in various tissues throughout the body, both adjacent to and distant from the tumor site. This DNA damage was dependent on CCL2, a cytokine involved in the recruitment and activation of macrophages, suggesting that this systemic DNA damage was mediated via tumor-induced chronic inflammatory responses involving cytokines, activation of macrophages, and consequent free radical production. If free radicals are involved, then a diet containing an antioxidant may decrease the distant DNA damage. Results Here we repeated our standard protocol in cohorts of two syngeneic tumor-bearing C57BL/6NCr mice that were on a Tempol-supplemented diet. We show that double-strand break and oxidatively-induced clustered DNA lesion levels were considerably decreased, about 2-3 fold, in the majority of tissues studied from the tumor-bearing mice fed the antioxidant Tempol compared to the control tumor-bearing mice. Similar results were also observed in nude mice suggesting that the Tempol effects are independent of functioning adaptive immunity. Conclusions This is the first in vivo study demonstrating the effect of a dietary antioxidant on abscopal DNA damage in tissues distant from a localized source of genotoxic stress. These findings may be important for understanding the mechanisms of genomic instability and carcinogenesis caused by chronic stress-induced systemic DNA damage and for developing preventative strategies.