Psychological precursors of epileptic seizures.

Psychological stress is the most commonly self-reported precursor of epileptic seizures. However, retrospective and prospective studies remain inconclusive in this regard. Here, we explored whether seizures would be preceded by significant changes in reported stressors or resource utilization. This study is based on high-frequency time series through daily online completion of personalized questionnaires of 9-24 items in epilepsy outpatients and compared responses 1-14 days before seizures with interictal time series. Fourteen patients (79% women, age = 23-64 years) completed daily questionnaires over a period of 87-898 days (median = 277 days = 9.2 months). A total of 4560 fully completed daily questionnaires were analyzed, 685 of which included reported seizure events. Statistically significant changes in preictal compared to interictal dynamics were found in 11 of 14 patients (79%) across 41 items (22% of all 187 items). In seven of 14 patients (50%), seizures were preceded by a significant mean increase of stressors and/or a significant mean decrease of resource utilization. This exploratory analysis of long-term prospective individual patient data on specific stressors and personal coping strategies generates the hypothesis that medium-term changes in psychological well-being may precede the occurrence of epileptic seizures in some patients.

Features of Self-Organization during the Process of Mindfulness-Based Stress Reduction: A Single Case Study.

Compared to the extensive evidence of the effectiveness of mindfulness-based interventions, there is only a limited understanding of their mechanisms of change. The three aims of this study are (1) to identify features of self-organization during the process (e.g., pattern transitions), (2) to obtain an impression of the effects of continuous self-assessments and feedback sessions on mindfulness-related stress reduction, and (3) to test the feasibility of high-frequency process monitoring and process feedback. Concerning aim (1), the specific hypothesis is that change will occur as a cascade of discontinuous pattern transitions emerging spontaneously in the sense of not being a reaction to external input. This single case study describes changing patterns of multiple time series that were produced by app-based daily self-assessments during and after an 8-week mindfulness-based stress reduction program. After this MBSR program, the participant (a female nurse) continued the self-assessment and the mindfulness practice for a further 10 months. The results confirm findings on the positive effects of mindfulness programs for healthcare professionals, especially on coping with work-related stress. The analysis of the time series data supports the hypothesis of self-organization as a possible mechanism of change manifesting as a cascade of phase transitions in the dynamics of a biopsychosocial system. At the end of the year, the participant reported a beneficial impact of daily monitoring and systematic feedback on the change process. The results underline the feasibility and usefulness of continuous high-frequency monitoring during and after mindfulness interventions.

Stability and flexibility in psychotherapy process predict outcome.

Ten good outcome and ten poor outcome psychotherapy cases were compared to investigate whether or not the temporal stability and flexibility of their process variables can predict their outcomes. Each participant was monitored daily using the Therapy Process Questionnaire (TPQ), which has 43 items and seven sub-scales, and responses over time were analyzed in terms of correlation robustness and correlation variability across the TPQ sub-scales. "Correlation robustness" and "correlation variability" are two basic characteristics of any correlation matrix: the first is calculated as the sum of the absolute values of Pearson correlation coefficients, the second as the standard deviation of Pearson correlation coefficients. The results demonstrated that the patients within the poor outcome group had lower values on both variables, suggesting lower stability and flexibility. Furthermore, a higher number of cycles of increase and decrease in correlation robustness and variability of the TPQ sub-scales was observed within good outcome psychotherapies, suggesting that, these cycles can be considered as process-markers of good-outcomes. These results provide support for the validity of these quantitative process-parameters, correlation robustness and variability, in predicting psychotherapeutic outcomes. Moreover, the results lend support to the common clinical experience of alternating periods of flexibility and integration being beneficial to good psychotherapeutic processes.

Detecting pattern transitions in psychological time series - A validation study on the Pattern Transition Detection Algorithm (PTDA).

With the increasing use of real-time monitoring procedures in clinical practice, psychological time series become available to researchers and practitioners. An important interest concerns the identification of pattern transitions which are characteristic features of psychotherapeutic change. Change Point Analysis (CPA) is an established method to identify the point where the mean and/or variance of a time series change, but changes of other and more complex features cannot be detected by this method. In this study, an extension of the CPA, the Pattern Transition Detection Algorithm (PTDA), is optimized and validated for psychological time series with complex pattern transitions. The algorithm uses the convergent information of the CPA and other methods like Recurrence Plots, Time Frequency Distributions, and Dynamic Complexity. These second level approaches capture different aspects of the primary time series. The data set for testing the PTDA (300 time series) is created by an instantaneous control parameter shift of a simulation model of psychotherapeutic change during the simulation runs. By comparing the dispersion of random change points with the real change points, the PTDA determines if the transition point is significant. The PTDA reduces the rate of false negative and false positive results of the CPA below 5% and generalizes its application to different types of pattern transitions. RQA quantifiers also can be used for the identification of nonstationary transitions in time series which was illustrated by using Determinism and Entropy. The PTDA can be easily used with Matlab and is freely available at Matlab File Exchange (https://www.mathworks.com/matlabcentral/fileexchange/80380-pattern-transition-detection-algorithm-ptda).

What makes inpatient treatment for PTSD effective? Investigating daily therapy process factors.

OBJECTIVE: Therapeutic process factors including alliance and motivation are considered to play a key role in the treatment of post-traumatic stress disorder (PTSD). Yet, our understanding of change processes in therapy is mostly based on theoretical considerations with limited empirical evidence. In order to identify process characteristics of successful inpatient treatments of PTSD, we investigated the intraindividual, interindividual, and temporal associations of daily assessments of therapy process factors like motivation, alliance, and insight. METHOD: Therapy process questionnaire (TPQ) assessments were collected from 101 inpatients with PTSD over 50 days, resulting in 5050 assessments. Multilevel vector autoregressive (mlVAR) modelling was applied to investigate the networks of the TPQ factors in a subgroup with good outcome regarding PTSD symptomatology and a subgroup with less favourable outcome. RESULTS: The two subgroups differed markedly in their network models, suggesting that therapy processes might be different for those with good and those with poor treatment outcomes. CONCLUSIONS: Our results suggest that good treatment outcome is linked to a specific therapy process dynamic where mindfulness and insight lead to the kind of temporary well-being required to effectively engage with problems and negative emotions, while motivation to change ensures the continuity of confronting negative emotions and problems.

Pathologically reduced neural flexibility recovers during psychotherapy of OCD patients.

Flexibility is a key feature of psychological health, allowing the individual to dynamically adapt to changing environmental demands, which is impaired in many psychiatric disorders like obsessive-compulsive disorder (OCD). Adequately responding to varying demands requires the brain to switch between different patterns of neural activity, which are represented by different brain network configurations (functional connectivity patterns). Here, we operationalize neural flexibility as the dissimilarity between consecutive connectivity matrices of brain regions (jump length). In total, 132 fMRI scans were obtained from 17 patients that were scanned four to five times during inpatient psychotherapy, and from 17 controls that were scanned at comparable time intervals. Significant negative correlations were found between the jump lengths and the symptom severity scores of OCD, depression, anxiety, and stress, suggesting that high symptom severity corresponds to inflexible brain functioning. Further analyses revealed that impaired reconfiguration (pattern stability) of the brain seems to be more related to general psychiatric impairment rather than to specific symptoms, e.g., of OCD or depression. Importantly, the group × time interaction of a repeated measures ANOVA was significant, as well as the post-hoc paired t-tests of the patients (first vs. last scan). The results suggest that psychotherapy is able to significantly increase the neural flexibility of patients. We conclude that psychiatric symptoms like anxiety, stress, depression, and OCD are associated with an impaired adaptivity of the brain. In general, our results add to the growing evidence that dynamic functional connectivity captures meaningful properties of brain functioning.

Long-Term Effects of Home-Based Family Therapy for Non-responding Adolescents With Psychiatric Disorders. A 3-Year Follow-Up.

OBJECTIVE: Home-based treatment of families with low socio-economic status and multiple psychosocial problems (multi-problem families, MPFs) is gaining importance in clinical social epidemiology and health services research. The sustainability of the treatment is of special importance in order to breach transgenerational effects. METHODS: We examined outcome, effect size, and clinical significance of home-based treatment for 84 multi-problem families in a naturalistic setting. 48 of the families were available for a follow-up after 3 years. The baseline characteristics of these family systems included low collaboration, an increased family adversity index, minors with high rates of child psychiatric disorders, a high prevalence of comorbidity, low relational family functioning, and adolescents who refused any form of treatment or had unilaterally terminated different forms of treatment before. The home-based family therapy consisted of one or two face-to-face counseling sessions per week over an average of 28.8 months (SD = 19.2). The symptoms and competence of the adolescents, the caregivers, and the family structure were assessed with 13 variables. RESULTS: All variables showed significant improvement rates (pre- vs. post- treatment) with medium to high effect sizes (mean of Cohen's d = 1.04, range = 0.34 - 2.18). All variables showed a sustained or even further improvement at follow-up. CONCLUSION: This study provides evidence of statistically (p), practically (d), and clinically (RCI) significant changes in symptom and competence-related variables among adolescents and caregivers in MPFs with sustainable long-term effects in the 3-year follow-up period.

Multi-level assessment of obsessive-compulsive disorder (OCD) reveals relations between neural and neurochemical levels.

BACKGROUND: While considerable progress has been made in exploring the psychological, the neural, and the neurochemical dimensions of OCD separately, their interplay is still an open question, especially their changes during psychotherapy. METHODS: Seventeen patients were assessed at these three levels by psychological questionnaires, fMRI, and venipuncture before and after inpatient psychotherapy. Seventeen controls were scanned at comparable time intervals. First, pre/post treatment changes were investigated for all three levels separately: symptom severity, whole-brain and regional activity, and the concentrations of cortisol, serotonin, dopamine, brain-derived neurotrophic factor (BDNF), and immunological parameters (IL-6, IL-10, TNFα). Second, stepwise linear modeling was used to find relations between the variables of the levels. RESULTS: The obsessive-compulsive, depressive, and overall symptom severity was significantly reduced after psychotherapy. At the neural level, the activity in the anterior cingulate cortex (ACC), in frontal regions, in the precuneus, and in the putamen had significantly decreased. No significant changes were found on the neurochemical level. When connecting the levels, a highly significant model was found that explains the decrease in neural activity of the putamen by increases of the concentrations of cortisol, IL-6, and dopamine. CONCLUSION: Multivariate approaches offer insight on the influences that the different levels of the psychiatric disorder OCD have on each other. More research and adapted models are needed.

Convergent Validation of Methods for the Identification of Psychotherapeutic Phase Transitions in Time Series of Empirical and Model Systems.

AIM: In many cases, the dynamics of psychotherapeutic change processes is characterized by sudden and critical transitions. In theoretical terms, these transitions may be "phase transitions" of self-organizing nonlinear systems. Meanwhile, a variety of methods is available to identify phase transitions even in short time series. However, it is still an open question if different methods for timeseries analysis reveal convergent results indicating the moments of critical transitions and related precursors. METHODS AND PROCEDURES: Seven concepts which are commonly used in nonlinear time series analysis were investigated in terms of their ability to identify changes in psychological time series: Recurrence Plots, Change Point Analysis, Dynamic Complexity, Permutation Entropy, Time Frequency Distributions, Instantaneous Frequency, and Synchronization Pattern Analysis, i.e., the dynamic inter-correlation of the system's variables. Phase transitions were simulated by shifting control parameters in the Hénon map dynamics, in a simulation model of psychotherapy processes (one by an external shift of the control parameter and one created by a simulated control parameter shift), and three sets of empirical time series generated by daily self-ratings of patients during the treatment. RESULTS: The applied methods showed converging results indicating the moments of dynamic transitions within an acceptable tolerance. The convergence of change points was confirmed statistically by a comparison to random surrogates. In the three simulated dynamics with known phase transitions, these could be identified, and in the empirical cases, the methods converged indicating one and the same transition (possibly the phase transitions of the cases). Moreover, changes that did not manifest in a shift of mean or variance could be detected. CONCLUSION: Changes can occur in many different ways in the psychotherapeutic process. For instance, there can be very slow and small transitions or very high and sudden ones. The results show the validity and stability of different measures indicating pattern transitions and/or early warning signals of those transitions. This has profound implications for real-time monitoring in psychotherapy, especially in cases where a transition is not obvious to the eye. Reliably identifying points of change is mandatory also for research on precursors, which in turn can help improving treatment.

The Therapy Process Questionnaire - Factor analysis and psychometric properties of a multidimensional self-rating scale for high-frequency monitoring of psychotherapeutic processes.

Many outcome measures and session-related questionnaires in psychotherapy are designed for weekly or biweekly administration. Yet, today, technical developments allow for higher frequency assessments to monitor human change dynamics more closely by daily assessments. For this purpose, the Therapy Process Questionnaire (TPQ) was developed, with a specific focus on inpatient psychotherapy. In this article, we present an explorative and confirmative factor analysis of the TPQ on the basis of the time series data of 150 patients collected during their hospital stay (mean time series length: 69.1 measurement points). A seven-factor solution was identified, which explains 68.7% of variance and associates 43 items onto the factors, which are "well-being and positive emotions," "relationship with fellow patients," "therapeutic relationship and clinical setting," "emotional and problem intensity," "insight/confidence/therapeutic progress," "motivation for change," and "mindfulness/self-care." The internal consistency (Cronbach's α), the inter-item correlations of the subscales, and the discriminative power of the items are excellent. The TPQ can be applied in practice and research for creating time series with equidistant measurement points and time series lengths, which are appropriate for the application of nonlinear analysis methods. Especially in clinical practice, it is important to identify precursors of phase transitions, changing synchronization patterns, and critical or instable periods of a process, which now is possible by internet- or app-based applications of this multidimensional questionnaire.

Erroneously Disgusted: fMRI Study Supports Disgust-Related Neural Reuse in Obsessive-Compulsive Disorder (OCD).

Objective: fMRI scans of patients with obsessive-compulsive disorder (OCD) consistently show a hyperactivity of the insular cortex, a region responsible for disgust-processing, when confronted with symptom-triggering stimuli. This asks for an investigation of the role of disgust and the insula in OCD patients. Methods: Seventeen inpatients with OCD and 17 healthy controls (HC) underwent fMRI scanning. Whole-brain contrasts were calculated for "Disgust vs. Neutral" for both groups, plus an analysis of variance (ANOVA) to assess the interaction between group and condition. Additionally, the emotional dimensions of valence and arousal, along with the ability to cope, were assessed by picture ratings. Results: The picture ratings confirmed the patients' heightened sensitivity to disgust with higher values for arousal and inability to cope, but not for valence. fMRI scans revealed no hyperactivity of the insula in patients compared to controls for the condition "Disgust vs. Neutral," indicating no basic hypersensitivity to disgusting stimuli. Increased activity in the precuneus in controls for this condition might correspond to the downregulation of arousal. Conclusions: The absent differences in neural activity of the insula in patients compared to controls for the disgust-condition, but heightened activity for symptom-provoking conditions, suggests that the illness is due to an erroneous recruitment of the insula cortex for OCD-stimuli. The finding is interpreted within the framework of the neural reuse hypothesis.

A Nonlinear Dynamic Systems Model of Psychotherapy: First Steps Toward Validation and the Role of External Input.

Mathematical modeling and computer simulations are important means to understand the mechanisms of psychotherapy. The challenge is to design models which not only predict outcome, but simulate the nonlinear trajectories of change. Another challenge is to validate them with empirical data. We proposed a model on change dynamics which integrates five variables (order parameters) (therapeutic progress or success, motivation for change, problem severity, emotions, and insight) and four control parameters (capacity to enter a trustful cooperation and working alliance, cognitive competencies and mindfulness, hopefulness, behavioral resources). The control parameters modulate the nonlinear functions interrelating the variables. The evolution dynamics of the system is determined by a set of nine nonlinear difference equations, one for each variable and parameter. Here we outline how the model can be tested and validated by empirical time series data of the variables, by time series of the therapeutic alliance, and by assessing the input onto the system as it is perceived by the client. The parameters are measured by questionnaires at the beginning and at the end of the treatment. A key element of the validation algorithm is the adjustment of the parameter values as assessed by the questionnaires to model-specific parameter values by which the dynamics can be reproduced (calibration). The validation steps are illustrated by the data of a client who used an internet-based tool for high-frequency therapy monitoring (daily self-ratings). Especially after applying the input vector (interventions as experienced by the client) the similarity between the empirical and the model dynamics becomes evident. The averaged correlation between the empirical and the simulated dynamics across all variables is .41, after applying a short averaging mean window and eliminating an initial transient period, it is .62, varying between .47 and .81, depending on the variable. The discussion opens perspectives on the combination of mathematical modeling with real-time monitoring in order to realize data-driven simulations for short-term predictions and to estimate the effects of interventions before real interventions are applied.

Individual OCD-provoking stimuli activate disorder-related and self-related neuronal networks in fMRI.

For patients with Obsessive-Compulsive Disorder (OCD), whose triggers are highly idiosyncratic, individual stimulus material has been used in several fMRI studies. This study aims at comparing individual to standardized picture sets and at investigating a possible overlap of the former with the self-referential neuronal network. During fMRI-scanning, 17 inpatients with OCD and 17 healthy controls were exposed to pictures of their personal triggers, photographed in their domestic environments, to standardized pictures designed to provoke OCD symptoms, and to neutral pictures. Whole-brain analyses were calculated and the pictures were rated by both patients and controls with respect to valence, arousal, and coping. Patients rated the individualized stimuli lower in valence and coping and higher in arousal compared to controls, and also compared to standardized OCD- and neutral stimuli. The individual stimuli elicited neuronal activity in the cingulate cortex, hippocampus, insula, middle frontal/precentral gyrus, superior/inferior parietal lobe, and precuneus, while no group difference was detected by the standardized OCD-stimuli. In conclusion, individual picture sets facilitate the detection of neuronal activity, but the results might be confounded due to the overlap with the network of self-referential processing and memory retrieval. The use of individual symptom-provoking and individual neutral stimuli would therefore be optimal.

Integrating the systematic assessment of psychological states in the epilepsy monitoring unit: Concept and compliance.

BACKGROUND: Admission to the epilepsy monitoring unit (EMU) for long-term video-electroencephalography (EEG) monitoring (VEEG) constitutes the gold standard for seizure diagnosis and presurgical evaluation. This study applied the concept of a high-frequency systematic monitoring of psychological states and tested patients' compliance in order to evaluate if its integration in the EMU is feasible and if patients benefit from the graphically underpinned discussion of their EMU stay-related cognitions and emotions. METHODS: The process-monitoring is technically realized by an internet-based device for data collection and data analysis, the Synergetic Navigation System (SNS). A convenient sample was enrolled: All eligible patients who were admitted to the EMU of the Department of Neurology, Christian Doppler Medical Center, Salzburg, Austria, between November 6th 2017 and January 26th 2018 were approached and recruited upon consent. After a short resource-oriented interview, each enrolled patient was provided with a tablet. The daily questionnaire included eight standardized and up to three personalized items. Self-assessments were collected every 5 h prior to meal times (6:30 am, 11:30 am, and 4:30 pm) and at 9:30 pm. The detailed visualizations of the patients' replies were discussed with the participants during a feedback session at the end of the EMU stay. RESULTS: Twenty-one patients (12 women/9 men, median age 29 years [range 18-74 years]) were consecutively recruited (72% of all eligible patients). Compliance rates were high (median: 82%, range 60%-100%) among the respondents. Mood correlated strongly with hopefulness (r = 0.71) and moderately with energy (r = 0.63) in all patients. When correlating the intraindividual medians of the process questionnaire time series with the pretest total scores, energy correlated moderately and negatively with the Perceived Stress Scale (PSS) (r = -0.45), while self-efficacy correlated moderately and negatively with the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) total scores in all patients (r = -0.5). Nine patients (43%) reported that they learned something meaningful about themselves after the feedback discussion of their individual time series. CONCLUSION: The results support the feasibility of high-frequency monitoring of psychological states and processes in routine EMU settings. Repeated daily collections four times per day of psychological surveys allow for the assessment of highly resolved, equidistant time series data, which gives insight into psychological states and processes during EMU admission.

Personality development in psychotherapy: a synergetic model of state-trait dynamics.

Theoretical models of psychotherapy not only try to predict outcome but also intend to explain patterns of change. Studies showed that psychotherapeutic change processes are characterized by nonlinearity, complexity, and discontinuous transitions. By this, theoretical models of psychotherapy should be able to reproduce these dynamic features. Using time series derived from daily measures through internet-based real-time monitoring as empirical reference, we earlier presented a model of psychotherapy which includes five state variables and four trait variables. In mathematical terms, the traits modulate the shape of the functions which define the nonlinear interactions between the variables (states) of the model. The functions are integrated into five coupled nonlinear difference equations. In the present paper, we model how traits (dispositions or competencies of a person) can continuously be altered by new experiences and states (cognition, emotion, behavior). Adding equations that link states to traits, this model not only describes how therapeutic interventions modulate short-term change and fluctuations of psychological states, but also how these can influence traits. Speaking in terms of Synergetics (theory of self-organization in complex systems), the states correspond to the order parameters and the traits to the control parameters of the system. In terms of psychology, trait dynamics is driven by the states-i.e., by the concrete experiences of a client-and creates a process of personality development at a slower time scale than that of the state dynamics (separation of time scales between control and order parameter dynamics).

Psychotherapy Is Chaotic-(Not Only) in a Computational World.

Objective: The aim of this article is to outline the role of chaotic dynamics in psychotherapy. Besides some empirical findings of chaos at different time scales, the focus is on theoretical modeling of change processes explaining and simulating chaotic dynamics. It will be illustrated how some common factors of psychotherapeutic change and psychological hypotheses on motivation, emotion regulation, and information processing of the client's functioning can be integrated into a comprehensive nonlinear model of human change processes. Methods: The model combines 5 variables (intensity of emotions, problem intensity, motivation to change, insight and new perspectives, therapeutic success) and 4 parameters into a set of 5 coupled nonlinear difference equations. The results of these simulations are presented as time series, as phase space embedding of these time series (i.e., attractors), and as bifurcation diagrams. Results: The model creates chaotic dynamics, phase transition-like phenomena, bi- or multi-stability, and sensibility of the dynamic patterns on parameter drift. These features are predicted by chaos theory and by Synergetics and correspond to empirical findings. The spectrum of these behaviors illustrates the complexity of psychotherapeutic processes. Conclusion: The model contributes to the development of an integrative conceptualization of psychotherapy. It is consistent with the state of scientific knowledge of common factors, as well as other psychological topics, such as: motivation, emotion regulation, and cognitive processing. The role of chaos theory is underpinned, not only in the world of computer simulations, but also in practice. In practice, chaos demands technologies capable of real-time monitoring and reporting on the nonlinear features of the ongoing process (e.g., its stability or instability). Based on this monitoring, a client-centered, continuous, and cooperative process of feedback and control becomes possible. By contrast, restricted predictability and spontaneous changes challenge the usefulness of prescriptive treatment manuals or other predefined programs of psychotherapy.

Systemic Case Formulation, Individualized Process Monitoring, and State Dynamics in a Case of Dissociative Identity Disorder.

Objective: The aim of this case report is to demonstrate the feasibility of a systemic procedure (synergetic process management) including modeling of the idiographic psychological system and continuous high-frequency monitoring of change dynamics in a case of dissociative identity disorder. The psychotherapy was realized in a day treatment center with a female client diagnosed with borderline personality disorder (BPD) and dissociative identity disorder. Methods: A three hour long co-creative session at the beginning of the treatment period allowed for modeling the systemic network of the client's dynamics of cognitions, emotions, and behavior. The components (variables) of this idiographic system model (ISM) were used to create items for an individualized process questionnaire for the client. The questionnaire was administered daily through an internet-based monitoring tool (Synergetic Navigation System, SNS), to capture the client's individual change process continuously throughout the therapy and after-care period. The resulting time series were reflected by therapist and client in therapeutic feedback sessions. Results: For the client it was important to see how the personality states dominating her daily life were represented by her idiographic system model and how the transitions between each state could be explained and understood by the activating and inhibiting relations between the cognitive-emotional components of that system. Continuous monitoring of her cognitions, emotions, and behavior via SNS allowed for identification of important triggers, dynamic patterns, and psychological mechanisms behind seemingly erratic state fluctuations. These insights enabled a change in management of the dynamics and an intensified trauma-focused therapy. Conclusion: By making use of the systemic case formulation technique and subsequent daily online monitoring, client and therapist continuously refer to detailed visualizations of the mental and behavioral network and its dynamics (e.g., order transitions). Effects on self-related information processing, on identity development, and toward a more pronounced autonomy in life (instead of feeling helpless against the chaoticity of state dynamics) were evident in the presented case and documented by the monitoring system.

First clinical release of an online, adaptive, aperture-based image-guided radiotherapy strategy in intensity-modulated radiotherapy to correct for inter- and intrafractional rotations of the prostate.

PURPOSE: We developed and evaluated a correction strategy for prostate rotations using direct adaptation of segments in intensity-modulated radiotherapy (IMRT). METHOD AND MATERIALS: Implanted fiducials (four gold markers) were used to determine interfractional translations, rotations, and dilations of the prostate. We used hybrid imaging: The markers were automatically detected in two pretreatment planar X-ray projections; their actual position in three-dimensional space was reconstructed from these images at first. The structure set comprising prostate, seminal vesicles, and adjacent rectum wall was transformed accordingly in 6 degrees of freedom. Shapes of IMRT segments were geometrically adapted in a class solution forward-planning approach, derived within seconds on-site and treated immediately. Intrafractional movements were followed in MV electronic portal images captured on the fly. RESULTS: In 31 of 39 patients, for 833 of 1013 fractions (supine, flat couch, knee support, comfortably full bladder, empty rectum, no intraprostatic marker migrations >2 mm of more than one marker), the online aperture adaptation allowed safe reduction of margins clinical target volume-planning target volume (prostate) down to 5 mm when only interfractional corrections were applied: Dominant L-R rotations were found to be 5.3° (mean of means), standard deviation of means ±4.9°, maximum at 30.7°. Three-dimensional vector translations relative to skin markings were 9.3 ± 4.4 mm (maximum, 23.6 mm). Intrafractional movements in 7.7 ± 1.5 min (maximum, 15.1 min) between kV imaging and last beam's electronic portal images showed further L-R rotations of 2.5° ± 2.3° (maximum, 26.9°), and three-dimensional vector translations of 3.0 ±3.7 mm (maximum, 10.2 mm). Addressing intrafractional errors could further reduce margins to 3 mm. CONCLUSION: We demonstrated the clinical feasibility of an online adaptive image-guided, intensity-modulated prostate protocol on a standard linear accelerator to correct 6 degrees of freedom of internal organ motion, allowing safe and straightforward implementation of margin reduction and dose escalation.

Target splitting in radiation therapy for lung cancer: further developments and exemplary treatment plans.

BACKGROUND: Reporting further developments evolved since the first report about this conformal technique. METHODS: Technical progress focused on optimization of the quality assurance (QA) program, especially regarding the required work input; and on optimization of beam arrangements. RESULTS: Besides performing the regular QA program, additional time consuming dosimetric measurements and verifications no longer have to be accomplished.'Class solutions' of treatment plans for six patients with non-resected non-small cell lung cancer in locally advanced stages are presented. Target configurations comprise one central and five peripheral tumor sites with different topographic positions to hilus and mediastinum. The mean dose to the primary tumor is 81,9 Gy (range 79,2-90,0 Gy), to macroscopically involved nodes 61,2 Gy (range 55,8-63,0 Gy), to electively treated nodes 45,0 Gy. Treatments are performed twice daily, with fractional doses of 1,8 Gy at an interval of 11 hours. Median overall treatment time is 33 days. The set-up time at the linac does not exceed the average time for any other patient. CONCLUSION: Target splitting is a highly conformal and nonetheless non-expensive method with regard to linac and staff time. It enables secure accelerated high-dose treatments of patients with NSCLC.

A strategy for the use of image-guided radiotherapy (IGRT) on linear accelerators and its impact on treatment margins for prostate cancer patients.

BACKGROUND AND PURPOSE: In external beam radiotherapy of prostate cancer, the consideration of various systematic error types leads to wide treatment margins compromising normal tissue tolerance. We investigated if systematic set-up errors can be reduced by a set of initial image-guided radiotherapy (IGRT) sessions. PATIENTS AND METHODS: 27 patients received daily IGRT resulting in a set of 882 cone-beam computed tomographies (CBCTs). After matching to bony structures, we analyzed the dimensions of remaining systematic errors from zero up to six initial IGRT sessions and aimed at a restriction of daily IGRT for 10% of all patients. For threshold definition, we determined the standard deviations (SD) of the shift corrections and selected patients out of this range for daily image guidance. To calculate total treatment margins, we demanded for a cumulative clinical target volume (CTV) coverage of at least 95% of the specified dose in 90% of all patients. RESULTS: The gain of accuracy was largest during the first three IGRTs. In order to match precision and workload criteria, thresholds for the SD of the corrections of 3.5 mm, 2.0 mm and 4.5 mm in the left-right (L-R), cranial-caudal (C-C), and anterior-posterior (A-P) direction, respectively, were identified. Including all other error types, the total margins added to the CTV amounted to 8.6 mm in L-R, 10.4 mm in C-C, and 14.4 mm in A-P direction. CONCLUSION: Only initially performed IGRT might be helpful for eliminating gross systematic errors especially after virtual simulation. However, even with daily IGRT performance, a substantial PTV margin reduction is only achievable by matching internal markers instead of bony anatomical structures.