High-dose salvage intensity-modulated radiotherapy with or without androgen deprivation after radical prostatectomy for rising or persisting prostate-specific antigen: 5-year results.

BACKGROUND: Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70 Gy might result in improved outcome. OBJECTIVE: To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD). DESIGN, SETTING, AND PARTICIPANTS: Between 1999 and 2008, 136 patients were referred for HD-SIMRT with or without AD. The median follow-up was 5 yr. Indications for HD-SIMRT were persisting prostate-specific antigen (PSA) or a rising PSA following RP. All patients were irradiated at a single, tertiary, academic centre. AD was initiated on the basis of seminal vesicle invasion, preprostatectomy PSA >20 ng/ml, Gleason score ≥ 4+3 (n=43), or personal preference of the referring urologist (n=54). INTERVENTION: A median 76-Gy dose was prescribed to the RP bed using intensity-modulated radiotherapy (IMRT) in all patients. AD consisted of a luteinising hormone-releasing hormone analogue for 6 mo. MEASUREMENTS: Univariate and multivariate analyses were used to examine the influence of patient- and treatment-related factors on late toxicity, biochemical relapse-free survival (bRFS), and clinical relapse-free survival (cRFS). RESULTS AND LIMITATIONS: The 5-yr actuarial bRFS and cRFS were 56% and 86%, respectively. On multivariate analysis, the presence of perineural invasion at RP (hazard ratio [HR]: 6.19, p=0.001) and an increasing pre-SRT PSA (PSA 0.5 ng/ml: HR: 1; PSA 1-1.5 ng/ml: HR: 1.60, p=0.30; and PSA >1 ng/ml: HR: 2.70, p=0.02) were independent factors for a decreased bRFS. The addition of AD improved bRFS (HR: 0.33, p=0.005). On multivariate analysis, none of the variables was a predictor of cRFS. The 5-yr risk of grade 2-3 toxicity was 22% and 8% for genitourinary and gastrointestinal symptoms, respectively. CONCLUSIONS: IMRT allows for safe dose escalation to 76Gy with good bRFS.

Preliminary results on setup precision of prone-lateral patient positioning for whole breast irradiation.

PURPOSE: The aim of this study was to develop a rapid and reproducible technique for prone positioning and to compare dose-volume indices in prone and supine positions. METHODS AND MATERIALS: Eighteen patients underwent computed tomography imaging for radiotherapy planning in prone and supine position. Experience was gained in the first eight patients, which lead to modifications of the Horizon prone breast board (Civco Medical Solutions, Orange City, Iowa, USA) and the patient setup technique. A unilateral breast holder (U-BH) was developed (Van de Velde, Schellebelle, Belgium) to retract the contralateral breast away from the treated breast. The technique was then applied to an additional 10 patients. The setup precision was evaluated using daily cone-beam CT. RESULTS: Modifications to the breast board were made to secure a prone-lateral rather then a pure prone position. We evolved from a classical setup using laser marks on the patients' body to a direct breast setup using marks on the breast only. The setup precision of the direct positioning procedure with the modified breast board and the U-BH is comparable to supine setup data in the literature. Dose-volume indices for heart and lung show significantly better results for prone than for supine position, and dose homogeneity within the treated breast did not differ according to the treatment position. CONCLUSIONS: The setup precision of our prone-lateral positioning technique is comparable to supine data in literature. Our data show the advantage of prone radiotherapy to spare the lung and heart. Further research is necessary to reduce the duration of prone setup.

Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer.

PURPOSE: To determine the planning results and acute toxicity after hypofractionated intensity-modulated arc radiotherapy and androgen deprivation for lymph node metastasized (Stage N1) prostate cancer. METHODS AND MATERIALS: A total of 31 patients with Stage T1-T4N1M0 prostate cancer were treated with intensity-modulated arc radiotherapy and 3 years of androgen deprivation as primary treatment. The clinical target volume (CTV(p)) was the prostate and seminal vesicles. Elective lymph node areas ((e)) were delineated and expanded by 2 mm to create the CTV(e). The planning target volumes (PTV(p) and PTV(e)) were created using a three-dimensional expansion of the CTV(p) and CTV(e), respectively, of 7 mm. A median dose of 69.3 Gy and 50 Gy was prescribed to the PTV(p) and PTV(e) respectively, to be delivered in 25 fractions. Upper and lower gastrointestinal toxicity was scored using the Radiation Therapy Oncology Group toxicity and radiotherapy-induced lower intestinal toxicity scoring system. Genitourinary toxicity was scored using a combined Radiation Therapy Oncology Group, LENT-SOMA (late effects normal tissue-subjective, objective, management, analytic), and Common Toxicity Criteria toxicity scoring system. RESULTS: The median follow-up time was 3 months. The mean prescription dose to the CTV(p) and PTV(p) was 70.4 Gy and 68.6 Gy, respectively. The minimal dose to the CTV(e) and PTV(e) was 49.0 Gy and 47.0 Gy, respectively. No acute Grade 2 or greater gastrointestinal toxicity occurred. Fourteen patients developed acute Grade 2 lower gastrointestinal toxicity. Acute Grade 3 and 2 genitourinary toxicity developed in 2 and 14 patients, respectively. CONCLUSION: The results of our study have shown that hypofractionated intensity-modulated arc radiotherapy as primary therapy for N1 prostate cancer is feasible with low toxicity.

Brain activation associated with deep brain stimulation causing dissociation in a patient with Tourette's syndrome.

Dissociation involves a disruption in the integrated functions of consciousness, memory, identity, or perception of the environment. Attempts at localizing dissociative responses have yielded contradictory results regarding brain activation, laterality, and regional involvement. Here, we used a single-day split-dose activation paradigm with single photon emission computed tomography and 99m-Tc ethylcysteinatedimer as a brain perfusion tracer in a patient with Tourette's syndrome undergoing bilateral high-frequency thalamic stimulation for the treatment of tics who developed an alternate personality state during right thalamic stimulation. We documented increased regional cerebral blood flow in bilateral prefrontal and left temporal brain areas during the alternate identity state. We conclude that our findings support the temporal lobe as well as the frontolimbic disconnection hypotheses of dissociation.

Measurement techniques, modeling strategies and pitfalls to avoid when implementing a mini MLC in a non dedicated planning system.

BACKGROUND AND PURPOSE: Ghent University Hospital investigated the feasibility of the Pinnacle system for planning intracranial stereotactic treatments. The aim was to perform precise dose computation using the collapsed cone engine for treatment delivery with the Moduleaf mini-MLC mounted on an Elekta accelerator. MATERIAL AND METHODS: The Moduleaf was commissioned using dose rate corrected data recorded by a diamond detector and using data measured by cylindrical chambers each limited to restricted field sizes. RESULTS: Automatic modeling resulted in clinical relevant dose errors up to 10%. Using manual modeling in Pinnacle, for clinical applicable fields a 2%/2 mm agreement between modeled data and measurements was obtained. CONCLUSION: The overall accuracy of the collapsed cone algorithm is within tolerances for single fraction stereotactic treatments.

Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

Does regional brain perfusion correlate with eating disorder symptoms in anorexia and bulimia nervosa patients?

OBJECTIVE: Using single photon emission computed tomography (SPECT), we sought brain perfusion correlates of eating disorder symptoms in anorexia and bulimia nervosa patients. METHOD: We investigated 67 female eating disordered (ED) patients. Eating disorder symptoms were measured by the Eating Disorders Inventory (EDI). Determination of brain areas in which regional perfusion co-varied with drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness and maturity fears was done by open explorative correlation analysis using Statistical Parametrical Mapping (SPM). RESULTS: A significant positive correlation between scores on body dissatisfaction and ineffectiveness, and brain perfusion in the prefrontal and parietal cortex was demonstrated. There were no correlations between other eating disorder symptoms and brain perfusion. CONCLUSION: Based on the finding of an association between regional brain flow and body dissatisfaction and ineffectiveness, we argue that neurobiological findings in ED patients may not only reflect emotional and behavioural factors but cognitive-evaluative features as well.

Differences of cortical 5-HT2A receptor binding index with SPECT in subtypes of anorexia nervosa: relationship with personality traits?

OBJECTIVE: Using single photon emission computed tomography and the 5-HT2A receptor antagonist, 123I-5-I-R91150, we explored differences in 5-HT2A binding index in anorexia nervosa patients with and without bulimic features. We also searched for associations between temperament dimensions and cortical 5-HT2) binding. METHOD: About 9 restrictive and 7 bulimic anorexia nervosa patients were examined and cortical 123I-5-I-R91150 binding index values were compared between the two subgroups. Open explorative correlation analysis was used to examine any relationships between binding index values and temperament scores, as assessed with the Temperament and Character Inventory. RESULTS: 5-HT2A binding index was significantly reduced in the parietal cortex in bulimic anorexia nervosa patients in comparison with restrictive anorectics. Further, a positive correlation was documented between reward dependence and parietal 5-HT2A binding index across patients in the two subgroups. DISCUSSION: Restrictive anorexia nervosa patients differ from binging/purging anorexia nervosa patients on the basis of a reduced parietal 5-HT2A binding index in the latter. We speculate that the finding of a positive correlation between parietal 5-HT2A binding and reward dependence might reflect an association between these two variables, at least in anorexia nervosa patients.

Blunted prefrontal perfusion in depressed patients performing the Tower of London task.

Impairment of cognition is common in depression, and many tasks on which depressed patients are impaired are sensitive to frontal lobe dysfunction. Performance on the Tower of London (TOL) task, which includes setting up and maintaining multiple subgoals at the same time, has been shown to depend on intact prefrontal cortices. Single photon emission computed tomography (SPECT) with 99mTc-ethyl cysteinate dimer was used to compare cognitive activation in nine depressed patients and nine normal controls during performance of the TOL task. Planning times and accuracy were measured as performance parameters, and functional imaging data were analysed with statistical parametric mapping (SPM99) to determine significant voxel-wise differences in activation between the two groups. During activation, depressed patients were as accurate as controls but differed in that they spent more thinking time. These findings agree with the results of neuropsychological studies. Compared with the normal controls, depressed patients were characterized by a blunted perfusion response in the right middle frontal cortex [Brodmann area (BA) 6] and the left superior frontal gyrus (BA 9), and by increased perfusion in the right superior temporal gyrus (BA 21) and the insular cortex (BA 13). This study shows that a SPECT activation procedure using the TOL task under classical test conditions is feasible in depressed patients.

Detailed spatio-temporal solids concentration profiling during batch settling of activated sludge using a radiotracer.

In building and tuning good settling models for secondary clarifiers of wastewater treatment plants, there is a need for measured continuous solids concentration profiles during batch settling. Conventional measuring techniques have difficulties in recording this kind of data, either because they are invasive, or because of the low solids concentration and/or solids density of activated sludge. This paper investigates a novel non-invasive measurement technique borrowed from nuclear medicine, using a solids radiotracer and gamma cameras, to obtain solids concentration profiles during the batch settling of activated sludge, in a pilot-scale column with a height of 1m. The technique does not disturb the settling process, does not alter the settling characteristics, gives profiles every minute and every few millimeters, and is capable of measuring in a range of 0-25 g/l with high accuracy. Dynamic solids concentration profile measurements were performed for sludges of different wastewater treatment plants, and at different initial concentrations. The results show a quantitative representation of the settling process, and reveal hindered and compression settling.

Changes in cerebellar blood flow after manipulation of the cervical spine using Technetium 99m-ethyl cysteinate dimer.

BACKGROUND: Cervical spine manipulation is one of the many interventions practiced by health professionals to treat musculoskeletal disorders of the cervical spine. Although serious consequences of manipulation have been documented, the incidence is thought to be rare. More frequently, there may be minor transient side effects after manipulation of the cervical spine, such as headache, dizziness, and nausea. One of the hypothesis is that these side effects are caused by ischemia in the areas perfused by the vertebral arteries. OBJECTIVE: The purpose of this study was to investigate whether manipulation of the cervical spine can influence blood flow in the brain. METHODS: Single photon emission computed tomography was used to examine changes in regional cerebral blood flow caused by cervical spine manipulation (CSM) performed by a physiotherapist to 15 volunteers, using a 1-day split-dose Technetium 99m-ethyl cysteinate dimer single photon emission computed tomography activation paradigm. RESULTS: One brain region was identified showing a decreased regional cerebral blood flow after manipulation. This region was situated in the anterior lobe of the left cerebellum (-42, -48, -24). CONCLUSIONS: These findings suggest that cerebellar hypoperfusion may occur after CSM. This could explain why certain people experience headache, dizziness, or nausea after CSM. Further investigation into patient symptoms in the presence of cerebellar hypoperfusion and the possible link of these findings with other adverse reactions are warranted.

Brain perfusion SPECT in impulsivity-related personality disorders.

BACKGROUND: Impulsive behaviours in patients with cluster B personality disorders are associated with low glucose metabolism and regional cerebral blood flow in the frontal cortex and subcortical structures. The aim of this study is to confirm the presence of a particular pattern of brain perfusion in a sample of borderline (BPD) and anti-social personality disorder (ASPD) patients using brain perfusion single photon emission computed tomography (SPECT). METHODS: A brain perfusion SPECT study was performed in 37 patients with BPD or ASPD (and no Axis I diagnosis) and 34 healthy control participants. Data were acquired on a triple head Toshiba gamma camera. Scatter and attenuation correction was done. Reconstructed SPECT images were analyzed by Statistical Parametrical Mapping (SPM99). RESULTS: There were no significant differences in age and gender distributions between the patients and the healthy controls. With regard to the functional imaging results, patients were characterized by a reduced regional cerebral blood flow (rCBF) in right temporal and prefrontal brain areas, including the right lateral temporal cortex (BA 21), the right frontopolar cortex (BA 10) and the right ventrolateral prefontal cortex (BA 47). CONCLUSIONS: Patients with BPD and ASPD who showed impulsive behaviour have diminished rCBF in areas of the right prefrontal and temporal cortex.

Cognitive neuroactivation using SPECT and the Stroop Colored Word Test in patients with diffuse brain injury.

Psychomotor slowing in patients with diffuse brain injury frequently underlies impaired cognitive performance on neuropsychological tests, for example, the Stroop Colored Word test. The aim of the present study was to determine the neural basis associated with performance on the Stroop interference subtask in patients with diffuse brain injury. We hypothesized that patients would be slower than healthy controls, and that this would be associated with brain activations other than those seen in healthy subjects. Brain perfusion, using a split-dose activation paradigm with single photon emission tomography (SPECT) and the Stroop test, was assessed in 9 patients with diffuse brain injury. The Stroop interference score was calculated as a behavioral parameter, and functional imaging data were analyzed with statistical parametrical mapping (SPM99) to determine significant voxel-wise differences of activation between the control and the activation condition. Patients were impaired on the interference subtask of the Stroop test. Comparison of the SPECT data obtained during the activation condition with those obtained during the control condition by means of SPM showed significant activations in the left inferior parietal lobe, the right anterior cingulate extending into the right middle frontal gyrus and the right caudate, and the left posterior cingulate cortex. Patients with diffuse brain injury were slower than healthy controls on the interference subtask of the Stroop test, suggesting difficulty with resistance to distractions. This finding was associated with activation effects in posterior (mainly parietal) brain areas in addition with activation of previously observed anterior (mainly anterior cingulate) brain regions.

Application of a neuropsychological activation probe with SPECT: the 'Tower of London' task in healthy volunteers.

BACKGROUND: Human planning is a complex mental process that may be evaluated by the 'Tower of London' (TOL) task, which includes setting up and maintaining multiple subgoals at the same time. Although positron emission tomography and functional magnetic resonance imaging have provided reliable data on the recruitment of a neural network engaged in planning tasks, the experimental settings of these studies cannot be applied in clinical conditions. Hence, this study reports on the TOL task under classical neuropsychological test conditions using single photon emission computed tomography (SPECT) activation in 10 healthy subjects. METHODS: Participants first performed a control task and then an activation task, i.e., the TOL planning task In the planning task, subjects were required to change, in the minimum number of moves possible, an initial arrangement of beads to match a goal arrangement. Subjects solved a set of eight TOL problems of increasing difficulty. A control task was designed such that it eliminates planning abilities, which is the process of interest. Planning times and accuracy were measured as performance parameters and functional imaging data were analysed with statistical parametric mapping (SPM99) to determine significant voxel-wise activations between the planning task and the control task. RESULTS: Both overall and for each difficulty level, measures of accuracy were within the normal range. Similar results were found for the overall thinking time and thinking times of each difficulty level. That is, performance of the healthy subjects during the TOL task replicated the typical pattern of results found with appropriate control samples in the literature. Also, activation of the right prefrontal cortex was consistent with other functional imaging results, thereby validating the use of the TOL task in a SPECT activation paradigm. CONCLUSIONS: Based on the present study it may be concluded that the close resemblance of the test conditions of the SPECT activation procedure with those of the TOL task in the investigation room constitutes a major advantage for future application of the SPECT activation procedure in clinical conditions.

Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with 99mTc-ECD and 123I-5-I-R91150.

Impulsive aggression in dogs has an important impact on human public health. Better insight into the pathophysiology of this phenomenon could lead to more adequate diagnosis and treatment. Indirect in vivo research on peripheral body fluids and post-mortem studies in impulsive animals and humans indicate a deficient serotonergic system in general and disturbances in the serotonin-2A (5-HT2A) receptor in particular. In this study, brain perfusion and the 5-HT2A receptors were examined in impulsive, aggressive dogs, in comparison with a group of normally behaving animals. In order to decide which dogs to include in this study, owners were asked to describe the general behaviour of the dogs, the circumstances in which aggression occurred and their conduct during aggressive acts. Finally, 19 dogs were retained for this study, showing, according to different behavioural specialists, disinhibited dominance aggression. Functional imaging studies were performed on all these dogs. Single-photon emission tomography (SPET) was used to measure regional brain perfusion using technetium-99m labelled ethyl cysteinate dimer (ECD). The 5-HT2A receptor binding properties were investigated using the selective radioligand iodine-123 labelled 5-I-R91150. A significant increase in uptake of the 5-HT2A radioligand was noted in all cortical areas. No significant alterations were found in regional cortical perfusion, indicating that the increased binding index was not a consequence of increased tracer delivery. This study supports a role for the serotonergic system in canine impulsive aggression.

Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography.

Normal aging is associated with a decrease in number and size of neurons, loss of synapses and neuronal branching and with a reduced functioning neurotransmitter systems, such as the serotonergic system. These structural and functional alterations have important impact on the behavioural, cognitive and affective status of the individual. With the introduction of functional brain imaging in veterinary medicine, the canine brain can be examined in vivo, evaluating changes in perfusion, metabolism and neurotransmitter systems. Since cognitive decline is recognised in the aging dog, it was our aim to investigate whether age related changes concerning cerebral perfusion and binding index of the selective 5-HT2A receptor ligand 123I-5-I-R91150 could be found in the canine brain. A group of twelve normal, aging dogs, older than 96 months, was compared to a normal reference group (n = 12), younger than 96 months. SPET images were obtained, using the radiopharmaceutical 99mTc-N,N''-1,2-ethylene-diylbis-L-cysteine diethylester dihydrochloride (99mTc-ECD) for evaluation of the regional perfusion and the selective radioligand 123I-5-I-R91150 for visualization of the 5-HT2A receptor. Regional decrease of cerebral blood-flow was noted in the fronto- and temporocortical area and in the subcortical region. Age was negatively correlated with perfusion in the left and right fronto-cortical region. The binding index of the neuroreceptor radioligand was decreased in the fronto-cortical region, with a significant negative correlation with age in the right fronto-cortical area. No correlation was found between alteration of perfusion and binding index of the receptor ligand, suggesting that age related perfusion differences do not influence the binding of this radioligand. These results suggest that age related effects should be considered in functional canine brain imaging.

Toward clinical application of neuropsychological activation probes with SPECT: a spatial working memory task.

UNLABELLED: The concept of working memory is central to theories of human cognition, because it is essential to human skills such as decision making and deductive reasoning. Although PET and functional MRI have provided robust data on the recruitment of specific pathways in working memory tasks, the experimental settings of these studies may not be transferable to a clinical situation. Hence, to develop neuropsychological SPECT activation probes that are suitable for daily clinical practice, this study reports on a neuropsychological activation task of spatial working memory under classical neuropsychological test conditions in healthy subjects. METHODS: Reaction times and accuracy were measured as behavioral parameters and functional imaging data were analyzed with statistical parametric mapping to determine significant voxel-wise changes between the perception task and the memory task. RESULTS: Subjects reacted more slowly and performed less accurately during the memory task compared with the perception task, findings that are in keeping with other neuropsychological studies. Also, the overall pattern of brain activations revealed in our experiment is consistent with the data of the literature, thereby validating our test probe. CONCLUSION: From a practical viewpoint, the close resemblance of the test conditions of the SPECT procedure with those of the investigation room and the relative simplicity of the task under study probably constitute major advantages for future clinical application of the SPECT procedure in patients with cognitive impairments.