Initial results of a randomized phase III trial of high dose image guided radiation with or without androgen deprivation therapy for intermediate-risk prostate cancer.

BACKGROUND: Prior randomized studies have shown a survival benefit using combined androgen deprivation therapy (ADT) and radiation therapy for intermediate-risk prostate cancer. However, these studies either used low doses of radiation (66.6 Gy to isocenter) or imaged guidance was not available. This study reports the initial differences for high dose image guided radiation with or without ADT. METHODS: From 2012 to 2014, 56 patients were treated with and 60 patients without 6 months of ADT (N = 116) in our phase III randomized trial for intermediate-risk prostate cancer. The primary endpoints of the current analysis are Expanded Prostate Cancer Index Composite (EPIC) scores, International Prostate Symptom Score (IPSS) scores, and bowel or urinary adverse events (AEs, graded using CTCAE v4) with and without ADT. Treatment consisted of 81 Gy in 45 treatments (tx) or 100 Gy Pd-103 implant followed by 45 Gy in 25 tx with or without ADT. Cone-beam fiducial-based guidance was done. Statistical analysis included Fisher's exact test, chi-square test, and ANCOVA. RESULTS: Median follow-up for both groups was 2.6 years. Acute or chronic urinary and acute or chronic bowel toxicities were similar with or without ADT (acute urinary: 16 vs 25 G0-1, 39 vs 35 G2 and 1 vs 0 G3, p = 0.17; chronic urinary: 40 vs 45 G1 and 16 vs 15 G2 toxicities, p = 0.68; acute bowel: 56 vs 59 G1 and 0 vs 1 G2 toxicities, p = 0.99; chronic bowel: 56 vs 59 G1 and 0 vs 1 G2 toxicities, p = 0.99). One patient had grade 3 urinary AE (1/116 or 0.8%). No patient had grade 3 bowel AE. With the use of ADT, a temporary decline in the EPIC sexual (p = 0.004) and hormonal scores (p = 0.02) were seen for the first 3 to 6 months after the completion of radiation, but the scores recovered by 12 months. Brachytherapy plus external beam radiation was compared to external beam radiation alone; brachytherapy EPIC urinary irritative scores were temporarily lower at 3 months, 76 vs. 84 (p = 0.006), had higher IPSS scores at 3 months, 15 vs 12 (p = 0.01), and had increased acute urinary AEs (p<0.001). No difference in failures were seen with or without ADT or associated with the use of brachytherapy. SIGNIFICANCE: Low toxicity and minimal temporary bother as measured by EPIC and IPSS were seen in both arms. ADT was well-tolerated and associated with temporary changes.

Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson's Disease Brains Are Differentially Generated in Mammalian Cell Models.

Misfolding and aggregation of α-synuclein into toxic soluble oligomeric α-synuclein aggregates has been strongly correlated with the pathogenesis of Parkinson's disease (PD). Here, we show that two different morphologically distinct oligomeric α-synuclein aggregates are present in human post-mortem PD brain tissue and are responsible for the bulk of α-synuclein induced toxicity in brain homogenates from PD samples. Two antibody fragments that selectively bind the different oligomeric α-synuclein variants block this α-synuclein induced toxicity and are useful tools to probe how various cell models replicate the α-synuclein aggregation pattern of human PD brain. Using these reagents, we show that mammalian cell type strongly influences α-synuclein aggregation, where neuronal cells best replicate the PD brain α-synuclein aggregation profile. Overexpression of α-synuclein in the different cell lines increased protein aggregation but did not alter the morphology of the oligomeric aggregates generated. Differentiation of the neuronal cells into a cholinergic-like or dopaminergic-like phenotype increased the levels of oligomeric α-synuclein where the aggregates were localized in cell neurites and cell bodies.

The reported pain coping strategies of pediatric burn survivors-does a correlation exist between coping style and development of anxiety disorder?

Unresolved pediatric pain, both acute and chronic, has been associated with negative short- and long-term physical and mental health outcomes. This study sought to determine whether an association existed between self-reported pain coping skills and anxiety levels in a cohort of pediatric burn patients, and whether gender would influence their responses. The sample comprised burn-injured children in attendance at one of three mature burn camp sites. The self-report measures utilized included the 41-item Screen for Child Anxiety Related Disorders Child Version and the 39-item Pain Coping Questionnaire. Parental consent was obtained. A psychologist administered the measures. Participants included 187 youth, mean age 12.4 ± 2.4 years, girls (n = 89) boys (n = 98) with 67% reporting visible burn scars. Among boys, the use of Internalizing Coping Strategies was moderately correlated with elevated scores on Panic Disorder symptoms (r = .42, P < .001). Among girls, the use of Internalizing Coping Strategies was associated with elevated Generalized Anxiety (r = .51, P < .001), Panic Disorder (r = .46, P < .001), and Total Anxiety Symptom Scores (r = .49, P < .001). Those children who reported using Behavioral Distraction Strategies did not have any elevated anxiety scores. These findings suggest that burn-injured children, who employ Internalization as their pain coping strategy, may be more vulnerable to the development of long-term anxiety disorder, which, if left untreated may result in a negative psycho/social outcome. Applicability to Practice: Assessment of in-patient pediatric patients with the Pain Coping Questionnaire may help to identify children who are more likely to experience long-term anxiety. Future studies should seek to confirm these findings and determine whether improved pain management and early treatment of anxiety can help to diminish the long-term implications of unhelpful pain strategies and increased anxiety in burn-injured children.

Measuring the burden of pediatric burn injury for parents and caregivers: informed burn center staff can help to lighten the load.

This study sought to identify which commonly experienced burn-related issues parents/caregivers of burn-injured youth deemed most stressful, difficult, and disruptive during their child's initial acute burn care hospitalization, and following the child's discharge. Parents completed an 11-item survey, asking them to rate the difficulty of items regarding their child's burn injury. The scale was created by burn doctors, nurses, and psychologists with an average of 10.5 (SD ± 4.8) years of experience. Items selected were among common parental problems reported in the burn literature. Respondents included 69 parents/caregivers of previously hospitalized, burn-injured youth. The majority were mothers, n = 51 (74%), and n = 34 (49%) were Caucasian. The most represented age group was 37 to 45 years, n = 31 (45%). Children were on average, 6.04 years out from their initial injury. All parents reported their child's pain as the most difficult part of the injury, n = 69 (100%). The second most common issue was the child's first hospital stay. The other two items found to be "very hard" or "pretty hard" were the time spent away from their other children, and feelings of hopelessness in being unable to fix everything for their child. In this study, key parental problems occurred during the child's initial hospitalization. Burn staff cannot alleviate all problems, however, staff education regarding distressing problems faced by parents, as well as possible solutions, can be made available.

Burn-injured youth may be at increased risk for long-term anxiety disorders.

This study aimed to determine the prevalence of long-term anxiety disorder in burn-injured youth. It is well documented that inpatient pediatric burn patients experience heightened anxiety. However, the prevalence of anxiety disorder in pediatric burn survivors warrants further investigation. Participants completed the Screen for Anxiety Related Disorders, a 41-item self-report measuring anxiety disorder symptomatology. Respondents included 197 pediatric burn survivors, 105 boys, 92 girls, who were between 8 and 18 years of age; the mean age was 12.4 ± 2.4 years. Mean age at time of injury was 5.8 ± 3.7 years, with 79% of youth reporting visible scars. There were 77 participants (39%) who screened positive for a possible anxiety disorder with a total anxiety score ≥25, and 28% with a total mean score of ≥30, more specific to the likely presence of anxiety disorder. Nearly half of the participants (44%) reported symptoms indicating the presence of separation anxiety with a mean score of ≥5, and 28% had symptoms indicating the presence of panic disorder and school avoidance disorder. Significant sex differences were observed for anxiety, with girls scoring significantly higher than boys on total anxiety P ≤ .001 and on all four subscales. Youth attending burn camps for ≥5 years reported significantly lower anxiety scores. This study supports the screening of burn-injured youth for anxiety disorder and highlights the importance of educating parents and burn care professionals regarding the symptoms of anxiety disorders. This can help to ensure that pediatric burn survivors receive treatment when anxiety disorder symptoms are present. Screening appears to be especially important for girls.