An age-corrected matched-pair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer.

PURPOSE: To compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy. METHODS AND MATERIALS: Low- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan-Meier method. RESULTS: There were 384 patients with median followup of 2.0 years (0.5-6.1) for IG-IMRT and 2.0 years (0.5-8.7) for HDR. The median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p=0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p=0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p=0.79), and Grade 3 ED were 15% in both groups (p=0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p=0.70). No variables were predictive of Grade ≥2 ED following treatment. CONCLUSIONS: Rates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment.

Toxicities and costs of placing prophylactic and reactive percutaneous gastrostomy tubes in patients with locally advanced head and neck cancers treated with chemoradiotherapy.

BACKGROUND: We compared dependence rates, complications, toxicities, and costs associated with prophylactic versus reactive percutaneous endoscopic gastrostomy (PEG) tube placement. METHODS: One hundred ninety-three patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy were retrospectively reviewed. RESULTS: The 1-year and 2-year actuarial PEG tube dependence rate of the entire cohort was 24% and 13%, respectively. There was no difference in the PEG tube dependence rates between those placed prophylactically versus reactively. Patients who received a PEG tube reactively had a significantly higher stricture rate (p = .03) and aspiration rate (p < .001) compared to the prophylactic group. There were significantly fewer hospitalizations in the prophylactic group compared to the reactive group (p = .003). When accounting for both PEG placement and hospitalizations, the prophylactic approach was found to be more cost effective. CONCLUSION: PEG tubes placed prophylactically were associated with lower rates of strictures, aspirations, hospitalizations, and costs compared to those placed reactively.

Common classification schemes for PCB congeners and the gene expression of CYP17, CYP19, ESR1 and ESR2.

BACKGROUND: Reliable techniques to measure polychlorinated biphenyl (PCB) congeners make the clearer definition of their effects on human health possible. Given that PCBs are classified as endocrine disrupters, we sought to explore the expression of some key genes involved in sex steroid metabolism. OBJECTIVES: To examine common classification schemes of PCB congeners and determine whether exposure to groups classified by mechanism of action alter the gene expression (GE) of CYP17, CYP19, and ESR1 and ESR2. METHODS: GE and exposure to various classifications of lipid-adjusted PCB congeners were examined in 139 daughters of the Michigan Fisheaters' Cohort. Using mixed models analyses and adjusting for age, menopausal status, and current use of oral contraceptives and hormone replacement therapy, GE data were regressed on exposure to PCB congener groupings based on mechanism of action. RESULTS: Three novel findings are elucidated: first, that up-regulation of CYP19 expression is associated with exposure to PCB groupings containing dioxin-like, potentially anti-estrogenic, immunotoxic congeners, including PCB IUPAC #74, #105, #118, #138, #156, #157, #158, #167, and #170 from this cohort. Second, that exposure to similar congeners (PCB IUPAC #105, #156, #157, #158, and #167 in this cohort) but using a classification based solely on hormonal mechanisms of action is associated with increased expression of ESR2. Third, that increased expression of CYP17 is of borderline significance when associated with exposure to PCB IUPAC #118, #138, and #156. CONCLUSIONS: These findings are both counter-intuitive and intriguing. Rather than exhibiting anti-estrogenic effects alone, they suggest that these congeners up-regulate the major enzyme involved in estrogen synthesis and tend to confirm previous findings of links between AhR and ER signaling pathways. Replication of these findings, expansion of the number of genes examined, exploration of mixtures of environmental chemicals, and subsequent study of health outcomes in a larger cohort are future priorities.