Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation.

Background: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. Methods: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. Results: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. Conclusions: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.

Exploring the Relationship between Disordered Sleep and Mood in Male Anorexia Nervosa: An Actigraphy Study.

Eating disorders (EDs), including anorexia nervosa (AN), are severe psychological disorders that affect individuals' eating behaviours and body perception. Previous research has shown that people with EDs often report poorer sleep. Some literature has suggested that it is mood dysregulation that mediates the link between EDs and sleep. However, the majority of previous studies only focused on females, while male ED patients have been overlooked. Therefore, the present study aimed to investigate the relationships between EDs, mood, and sleep among male ED patients. Using a mixture of actigraphy recordings and self-reported questionnaires, the current study analysed a total 33 adult male participants diagnosed with AN. The participants first wore an actigraphy device for seven continuous days, following which their ED severity and mood were assessed by the Eating Disorder Examination Questionnaire (EDE-Q) and Depression Anxiety Stress Scale (DASS), respectively. The descriptive actigraphy results suggested that, similar to females, males with AN also showed disturbed sleep, including insomnia, sleep fragmentation, low sleep efficiency, and increased napping sessions. However, when ED severity was correlated against actigraphy data and mood, no significant relationships were found between them. Thus, it was suggested that future studies may investigate discrete ED symptoms instead of global ED severity interacting with sleep and mood. Overall, this study represents an initial step in the investigation of EDs and sleep and mood dysregulation among an under-represented sample.

Evaluating the prevalence and predictive factors of vasomotor and psychological symptoms in prostate cancer patients receiving hormonal therapy: Results from a single institution experience.

BACKGROUND & PURPOSE: The impact of vasomotor symptoms (VMS) occurring in prostate cancer (PC) patients whilst on androgen deprivation therapy (ADT) has not been extensively researched. This longitudinal study sought to assess the VMS and identify any predictive factors. MATERIAL & METHODS: Data from 250 PC patients on ADT were prospectively evaluated between January 10 and August 13 using a physician-directed questionnaire, to assess the impact of VMS. Parameters including height, weight, body surface area (BSA), body mass index (BMI), duration/type of ADT, co-morbidities and ethnicity were recorded. RESULTS: Fifty (20%) men reported no toxicity, whilst 171 (68.4%), and 29 (11.6%) reported mild to moderate and severe symptoms, respectively. Drenching sweats and hot flashes were common, and coexisted with sleep disturbances and fatigue. Patients with severe toxicity were younger (73 vs. 77 yrs; p = 0.04), had higher BMI (28 vs. 26; p = 0.02), and higher BSA (1.99 vs. 1.90; p = 0.04), when compared with those experiencing no toxicity. On multivariate analysis, younger age was predictive of sweats and hot flushes, whilst Afro-Caribbean men were twice as likely to experience sweats (OR 2.03, p = 0.05). CONCLUSIONS: The short-term side-effect profile of ADT for prostate cancer was favourable, though debilitating VMS can occur in a significant minority of cases. Younger age and higher BMI predicted for severe toxicity but not the duration of ADT.

Assessing intra-fractional bladder motion using cine-MRI as initial methodology for Predictive Organ Localization (POLO) in radiotherapy for bladder cancer.

AIM: To assess the feasibility of using cine-MR to study intra-fractional time-volume and volume-deformity patterns of the bladder during radiotherapy as initial methodology for Predictive Organ Localization (POLO). METHODS: Nine patients receiving radiotherapy for localized muscle invasive bladder cancer were prospectively studied. Each had an MR scan performed on an empty bladder using a T1 weighted cine sequence over a period of 20 min. Scans were taken prior to, and repeated towards the end of, radiotherapy treatment. Time-volume sequences were determined and compared before and during radiotherapy. Absolute bladder volumes were then correlated with changes in bladder wall position. RESULTS: The mean post void residual bladder volume prior to radiotherapy at time 0 was 113 cm(3) [SD 53] and this did not differ significantly during radiotherapy -106 cm [SD 40] (p=0.24, paired t-test analysis). A linear relationship was observed for the rate bladder filling over a 20 min period, which did not significantly change on the cine-MR during radiotherapy (regression coefficient 2.1 vs 1.6, respectively, p=0.51). Significant positive relationships were seen between volume and anterior (p=0.02), superior (p<0.001), and inferior (p=0.03) wall motion. These relationships were complex, though linearity was observed for volumes up to 150 cm(3). The 1.5 cm CTV-PTV margin was sufficient to account for expansion in the majority of cases with the only breach occurring on the anterior wall in one patient. CONCLUSIONS: This study confirms the feasibility of using cine-MR for POLO. The development of such predictive methodology may compensate for the need to use an isotropic CTV-PTV margin to simply cover bladder filling when using image-guided radiotherapy.

Evaluating the relationship between erectile dysfunction and dose received by the penile bulb: using data from a randomised controlled trial of conformal radiotherapy in prostate cancer (MRC RT01, ISRCTN47772397).

AIM: To evaluate the relationship between erectile function and the radiation dose to the penile bulb and other proximal penile structures in men receiving conformal radiotherapy (CFRT) for prostate cancer (PCa). METHODS: The Medical Research Council (MRC) RT01 trial randomised 843 men who had localised PCa to receive either 64 or 74 Gy after 3 - 6 months neoadjuvant hormonal treatment. Fifty-one men were selected who were potent prior to hormonal treatment, having completed both pre-hormone and 2-year post-CFRT Quality of Life assessments, and on whom dose volume data were available for analysis. The men were divided into three groups according to 2-year follow-up: potent, reduced potency, and impotent. The bulb of the penis together with the crura, were outlined on restored treatment plans. Dose - volume histograms were generated and compared between the three groups. An ordered logistic regression model was used to calculate the odds ratio of a range of dose - volume parameters to the penile bulb and effect on erectile dysfunction. The dose to the penile bulb was correlated to the dose received by the crura. RESULTS: Of the 51 patients, 12 remained potent, 22 had reduced potency, and 17 were impotent at 2 years. No differences were seen in mean dose to the penile bulb by allocated treatment (t test = 1.61, p = 0.11). The mean doses to the penile bulb received by the potent, reduced potency, and impotent groups were 45.5 Gy (SD 17.1), 48 Gy (SD 16.1), and 59.2 Gy (SD 13.8), respectively. There was a strong correlation between the mean dose received by the penile bulb and dose to the crura (r = 0.82, p < 0.0001). 83.3% of impotent patients received a D90 > or = 50 Gy to the penile bulb compared with 29.4% of patients who maintained potency at 2 years (p = 0.006). CONCLUSION: There is evidence from this study to suggest a dose volume effect on the penile bulb and erectile dysfunction. A D90 > or = 50 Gy is associated with a significant risk of erectile dysfunction and this should form a basis for selecting dose constraints in future dose escalation studies.

A comparison of CT- and ultrasound-based imaging to localize the prostate for external beam radiotherapy.

PURPOSE: This study assesses the accuracy of NOMOS B-mode acquisition and targeting system (BAT) compared with computed tomography (CT) in localizing the prostate. METHODS AND MATERIALS: Twenty-six patients were CT scanned, and the prostate was localized by 3 observers using the BAT system. The BAT couch shift measurements were compared with the CT localization. Six of the patients had gold markers present in the prostate, and the prostate movement determined by BAT was compared with the movement determined by the gold markers. RESULTS: Using the BAT system, the 3 observers determined the prostate position to be a mean of 1-5 mm over all directions with respect to the CT. The proportion of readings with a difference >3 mm between the observers was in the range of 25% to 44%. The prostate movement based on gold markers was an average of 3-5 mm different from that measured by BAT. The literature assessing the accuracy and reproducibility on BAT is summarized and compared with our findings. CONCLUSIONS: We have found that there are systematic differences between the BAT-defined prostate position compared with that estimated on CT using gold grain marker seeds.

Technological advances in radiotherapy for the treatment of localised prostate cancer.

There is good evidence that radiation dose escalation in localised prostate cancer is associated with increased cell kill. The traditional two-dimensional (2D) technique of treatment planning and delivery is limited by normal tissue toxicity, such that the dose that can be safely delivered to the prostate by external beam radiotherapy is 65-70 Gy. Several technological advances over the last 20 years have enhanced the precision of external beam radiotherapy (EBRT), and have resulted in improved outcomes. The three-dimensional conformal radiotherapy (3D-CRT) approach reduces the dose-limiting late side-effect of proctitis and has allowed for dose escalation to the whole prostate to 78 Gy. More recently, intensity modulated radiotherapy (IMRT), an advanced form of conformal therapy, has resulted in reduced rectal toxicity when using doses greater than 80 Gy. In addition, IMRT can potentially escalate the dose to specific parts of the prostate where there are resistant subpopulations of tumour clonogens, or can be used to extend the high-dose region to pelvic lymph nodes. The addition of androgen deprivation to conventional radiotherapy has an impact on survival and local control. Initial hormone therapy causes cytoreduction of the prostate cancer allowing for a reduction in radiotherapy volume as well as an additive effect on cell kill. Long-term adjuvant androgen deprivation has been shown to improve overall survival in more advanced tumours. Prostate brachytherapy is now a recognised treatment for those with low-risk disease. It achieves similar long-term outcome to other treatment modalities. Brachytherapy can be used as monotherapy for localised disease, or as boost treatment following conventional EBRT for locally advanced disease. New techniques are available to improve the precision of both target definition and treatment verification. This so-called image-guided radiotherapy will help to enhance the accuracy of dose delivery by correcting both for inter-fraction positional variation and for intra-fraction movement of the prostate in real-time and will allow for tighter tumour margins and avoidance of normal tissues, thereby enhancing the safety of treatment.