Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials.

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

Microbial growth and volatile organic compound (VOC) emissions from carpet and drywall under elevated relative humidity conditions.

BACKGROUND: Microbes can grow in indoor environments if moisture is available, and we need an improved understanding of how this growth contributes to emissions of microbial volatile organic compounds (mVOCs). The goal of this study was to measure how moisture levels, building material type, collection site, and microbial species composition impact microbial growth and emissions of mVOCs. We subjected two common building materials, drywall, and carpet, to treatments with varying moisture availability and measured microbial communities and mVOC emissions. RESULTS: Fungal growth occurred in samples at >75% equilibrium relative humidity (ERH) for carpet with dust and >85% ERH for inoculated painted drywall. In addition to incubated relative humidity level, dust sample collection site (adonis p=0.001) and material type (drywall, carpet, adonis p=0.001) drove fungal and bacterial species composition. Increased relative humidity was associated with decreased microbial species diversity in samples of carpet with dust (adonis p= 0.005). Abundant volatile organic compounds (VOCs) that accounted for >1% emissions were likely released from building materials and the dust itself. However, certain mVOCs were associated with microbial growth from carpet with dust such as C10H16H+ (monoterpenes) and C2H6SH+ (dimethyl sulfide and ethanethiol). CO2 production from samples of carpet with dust at 95% ERH averaged 5.92 mg hr-1 kg-1, while the average for carpet without dust at 95% ERH was 2.55 mg hr-1 kg-1. CONCLUSION: Microbial growth and mVOC emissions occur at lower relative humidity in carpet and floor dust compared to drywall, which has important implications for human exposure. Even under elevated relative humidity conditions, the VOC emissions profile is dominated by non-microbial VOCs, although potential mVOCs may dominate odor production. Video Abstract.