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- Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study. [JOURNAL ARTICLE]
- Prostate Cancer Prostatic Dis 2014 Aug 19.
BACKGROUND:To assess the relationship between androgen deprivation therapy (ADT) exposure and self-reported bone complications among men in a population-based cohort of prostate cancer survivors followed for 15 years after diagnosis.METHODS:The Prostate Cancer Outcomes Study enrolled 3533 patients diagnosed with prostate cancer between 1994 and 1995. This analysis included participants with non-metastatic disease at the time of diagnosis who completed 15-year follow-up surveys to report development of fracture, and use of bone-related medications. The relationship between ADT duration and bone complications was assessed using multivariable logistic regression models.RESULTS:Among 961 surviving men, 157 (16.3%) received prolonged ADT (>1 year), 120 (12.5%) received short-term ADT (⩽1 year) and 684 (71.2%) did not receive ADT. Men receiving prolonged ADT had higher odds of fracture (OR 2.5; 95% confidence interval (CI): 1.1-5.7), bone mineral density testing (OR 5.9; 95% CI: 3.0-12) and bone medication use (OR 4.3; 95% CI: 2.3-8.0) than untreated men. Men receiving short-term ADT reported rates of fracture similar to untreated men. Half of men treated with prolonged ADT reported bone medication use.CONCLUSIONS:In this population-based cohort study with long-term follow-up, prolonged ADT use was associated with substantial risks of fracture, whereas short-term use was not. This information should be considered when weighing the advantages and disadvantages of ADT in men with prostate cancer.Prostate Cancer and Prostatic Disease advance online publication, 19 August 2014; doi:10.1038/pcan.2014.31.
- Cardiovascular risk profile of veteran men beginning androgen deprivation therapy. [Journal Article]
- J Vasc Nurs 2014 Sep; 32(3):99-104.
We sought to describe the cardiovascular profile of veteran men before beginning androgen deprivation therapy (ADT), with the eventual benefit of targeting treatments to manage harmful cardiovascular side effects. We performed a secondary analysis with chi-square and Fisher's exact tests for associations between demographics and cardiovascular comorbidities on 375 veteran men diagnosed with prostate cancer. Those who were overweight and current smokers were more likely to be younger, whereas men with a systolic blood pressure >120 mmHg were more likely to be older (all P < 0.05). Men with total cholesterol 180 mg/dL were more likely to be identified in the Hispanic/other/unknown ethnicity category. Interventions to manage cardiovascular risk should focus on preventive lifestyle changes for younger men, and chronic disease management for older men. Men in the smaller Hispanic/other/unknown category are at risk for marginalization within the Veteran Administration system owing to their low numbers and should be closely monitored for cholesterol levels when receiving ADT.
- Association of Androgen Deprivation Therapy with Excess Cardiac-Specific Mortality in Men with Prostate Cancer. [JOURNAL ARTICLE]
- BJU Int 2014 Aug 15.
To determine if androgen deprivation therapy (ADT) is associated with excess cardiac-specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI).Five thousand seventy-seven men (median age, 69.5 years) with cT1c-T3N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant ADT (median duration, four months) between 1997 and 2006. Fine and Gray's competing risks analysis evaluated the association of ADT with CSM, adjusting for age, year of brachytherapy, and ADT treatment propensity score among men in groups defined by cardiac comorbidity.After a median follow-up of 4.8 years, no association was detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5 years for ADT vs 1.27% at five years for no ADT, adjusted hazard ratio (AHR) 0.83; 95% confidence interval (CI), 0.39-1.78; P=0.64; n=2653) or in men with diabetes mellitus, hypertension, or hypercholesterolemia (2.09% vs 1.97%, AHR, 1.33; 95% CI, 0.70-2.53; P=0.39; n=2168). However, ADT was associated with significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01-10.64; P=0.048; n=256). In this subgroup, the five-year cumulative incidence of CSM was 7.01% (95% CI 2.82-13.82%) for ADT vs 2.01% (95% CI 0.38-6.45%) for no ADT.ADT was associated with a five percent absolute excess risk of CSM at five years in men with CHF or prior MI, suggesting that administering ADT to 20 men in this potentially vulnerable subgroup could result in one cardiac death.
- Predictive clinical indicators of biochemical progression in advanced prostate cancer patients receiving leuplin depot as androgen deprivation therapy. [Journal Article]
- PLoS One 2014; 9(8):e105091.
Therapeutic planning and counseling for advanced prostate cancer patients receiving androgen deprivation therapy (ADT) is complicated because the prognoses are highly variable. The purpose of this study is to identify predictive clinical indicators of biochemical progression (BCP). In this retrospective analysis, data from 107 newly diagnosed patients (from November 1995 to April 2008) with advanced prostate adenocarcinoma receiving Leuprorelin acetate depot were analyzed. Data was collected from the computerized registry of two collaborating medical centers in Taiwan. Cox regression and Kaplan-Meier analyses were used to evaluate the relationship between potential predictive parameters and BCP. Univariate analysis revealed that predictors of BCP included (1) initial serum prostate-specific antigen (PSA) (hazard ratio [HR], 1.00; 95% confidence interval [CI] 1.00-1.00); (2) log of initial PSA (HR, 1.35; 95% CI 1.17-1.56); (3) PSA density at diagnosis (HR, 1.00; 95% CI 1.00-1.01), and (4) pathological bone fracture (HR, 2.22; 95% CI 1.20-4.11). Age (HR, 0.94; 95% CI 0.91-0.98) and hemoglobin levels (HR, 0.86; 95% CI 0.76-0.97) were also associated with greater risk of BCP. After adjusting for age, pathologic fracture, and hemoglobin level, the initial PSA and PSA density were no longer significantly associated with BCP. However, age and hemoglobin levels continued to be associated with greater risk of BCP (P≤0.007). Using Kaplan-Meier analysis, patients with higher initial PSA concentration, pathological bone fracture, and low hemoglobin had a greater probability of BCP. Thus, low hemoglobin and age are predictive indicators of BCP and therefore early indicators of BCP despite ADT therapy.
- Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy. [JOURNAL ARTICLE]
- Oncoimmunology 2014.:e29243.
Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen-deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure-free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT.
- A Structural and Spectroscopic Investigation of Octahedral Platinum Bis(dithiolene)phosphine Complexes: Platinum Dithiolene Internal Redox Chemistry Induced by Phosphine Association. [JOURNAL ARTICLE]
- Inorg Chem 2014 Aug 12.
The complexes [Pt(mdt)2] (4; mdt = methyldithiolene, [Me2C2S2](n-)), [Pt(adt)2] (5; adt = p-anisyldithiolene, [(MeO-p-C6H4)2C2S2](n-)), and [Pd(adt)2] (10) have been prepared in yields of ≥90% via transmetalation reactions with the corresponding [R2Sn(S2C2R'2)] complexes (R = (n)Bu, R' = Me; R = Me, R' = -C6H4-p-OMe, 3). Intraligand C-S and C-Cchelate bond lengths (∼1.71 and ∼1.40 Å, respectively) obtained by X-ray crystallography show these compounds to be comprised of radical monoanions mdt(•-) and adt(•-). The six-coordinate octahedral adducts [Pt(adt)2(dppe)] [6; dppe = 1,2-bis(diphenylphosphino)ethane], trans-[Pt(adt)2(PMe3)2] (8), and trans-[Pt(mdt)2(PMe3)2] (9) have also been prepared, and crystal structures reveal dithiolene ligands that are fully reduced ene-1,2-dithiolates (C-S and C-Cchelate = ∼1.77 and 1.35 Å, respectively). Reduction of the dithiolene ligand thus occurs to accommodate the +IV oxidation state typical of octahedral six-coordinate platinum. The cyclic voltammogram of 5 shows two fully reversible reductions at -0.11 and -0.84 V in CH2Cl2 (vs Ag/AgCl), attributed to successive (adt(•-) + e(-) → adt(2-)) processes, and a reversible oxidation at +1.01 V. The cyclic voltammogram of 9 shows two reversible oxidations at +0.38 and +0.86 V, which are assigned as successive (adt(2-) → adt(•-) + e(-)) oxidations. Consistent with their formulation as having fully reduced dithiolene ligands, the UV-vis spectra for 6, 8, and 9 show no low-energy absorptions below 700 nm, and the S K-edge XAS spectra of 6 and 8 show dithiolene sulfur that is reduced relative to that in 5. The introduction of PMe3 to 10 did not produce the palladium analogue of 8 but rather [Pd(adt)(PMe3)2] (11). The reaction of [PdCl2(PPh3)2] with Li2(mdt) produced a mixture of [Pd(mdt)(PPh3)2] (12, 20%) and [(Ph3P)Pd(μ-1,2-mdt-S,S':S)2Pd(PPh3)] (13, 28%), with the latter having C2 symmetry with a Pd2S2 core structure folded along the S···S axis.
- Strongly Correlated Alignment of Fluorinated 5,11-Bis(triethylgermylethynyl)anthradithiophene Crystallites in Solution-Processed Field-Effect Transistors. [JOURNAL ARTICLE]
- Chemphyschem 2014 Aug 8.
The crystallinity of an organic semiconductor film determines the efficiency of charge transport in electronic devices. This report presents a micro-to-nanoscale investigation on the crystal growth of fluorinated 5,11-bis(triethylgermylethynyl)anthradithiophene (diF-TEG-ADT) and its implication for the electrical behavior of organic field-effect transistors (OFETs). diF-TEG-ADT exhibits remarkable self-assembly through spin-cast preparation, with highly aligned edge-on stacking creating a fast hole-conducting channel for OFETs.
- Catheter Ablation and Anti-Arrhythmic Drug Therapy as First or Second Line Therapy in the Management of Atrial Fibrillation: A Systematic Review and Meta-Analysis. [JOURNAL ARTICLE]
- Circ Arrhythm Electrophysiol 2014 Aug 10.
-The optimal management of atrial fibrillation (AF) remains unclear. We performed a meta-analysis of randomized controlled trials (RCT) to examine the safety and efficacy of catheter ablation (CA) as compared to anti-arrhythmic drug therapy (ADT) both as first or second line therapy for the maintenance of sinus rhythm in AF.-Several databases were searched from inception through March 2014which yielded 11 studies with 1481 AF patients. The outcomes measured were recurrence of atrial tachyarrhythmia and the incidence of adverse events. A sub-group analysis was done to evaluate the efficacy of CA as first or second line therapy. There was recurrence of atrial tachyarrhythmia in 222 of 785 (28%) patients who underwent CA and in 451 of 696 (65%) patients who were on ADT (RR 0.40, 95% CI, 0.31-0.52, p = 0.00001). Sub-group analysis revealed a beneficial effect of CA both as a first line (RR 0.52, 95% CI, 0.30-0.91, p = 0.02) and as a second line (RR 0.37, 95% CI, 0.29-0.48, p<0.00001) therapeutic modality. There was a significantly higher incidence of major adverse events in the CA group compared with the ADT group (RR 2.04, 95% CI, 1.10 - 3.77, p = 0.02, I(2) = 0%).-CA appears to be superior to ADT in drug naïve, resistant and intolerant patients with AF. However, it should be performed in carefully selected patients after weighing the risks and benefits of the procedure.
- Role of Androgen Deprivation Therapy in Early Salvage Radiation Among Patients With Prostate-Specific Antigen Level of 0.5 or Less. [JOURNAL ARTICLE]
- Clin Genitourin Cancer 2014 Jun 27.
The Radiation Therapy Oncology Group 96-01 randomized trial demonstrated the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy for an increasing prostate-specific antigen (PSA) after prostatectomy, but it is unknown whether modern patients followed with ultrasensitive PSA and salvaged at a low PSA (ie, ≤ 0.5) also benefit from ADT.The cohort comprised 108 patients who received radical prostatectomy (RP), were followed by ultrasensitive PSA, and received salvage radiotherapy at a PSA of 0.5 or less. Sixty patients had negative margins, and 48 patients had positive margins at RP. Cox multivariable regression analysis was performed to identify factors associated with time to secondary PSA failure and included PSA at salvage, year of treatment, Gleason score, ADT use, margin status, T stage, and PSA doubling time. Occurrence of distant metastases was documented.Median follow-up after radiation was 63.09 months. A total of 24 patients had a distant metastasis. In all patients, ADT use was associated with a decreased risk of recurrence (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.79; P = .006). On subgroup analysis, ADT was associated with a decreased risk of failure among patients with negative margins (HR, 0.27; 95% CI, 0.12-0.61; P = .002), but not among men with positive margins (HR, 0.78; 95% CI, 0.29-2.10; P = .63).Even patients followed with ultrasensitive PSA and salvaged early with a PSA ≤ 0.5 seem to benefit from the addition of ADT to salvage radiation. However, this benefit seemed to be limited to men with negative margins; thus, men with positive margins and PSA ≤ 0.5 may be good candidates for salvage radiation alone.
- Adverse Effects of Androgen Deprivation Therapy and Strategies to Mitigate Them. [REVIEW]
- Eur Urol 2014 Aug 2.
Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition.To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT.The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects.Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin).ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects.Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.