EviGUIDE - a tool for evidence-based decision making in image-guided adaptive brachytherapy for cervical cancer

PURPOSE: To develop a novel decision-support system for radiation oncology that incorporates clinical, treatment and outcome data, as well as outcome models from a large clinical trial on magnetic resonance image-guided adaptive brachytherapy (MR-IGABT) for locally advanced cervical cancer (LACC). METHODS: A system, called EviGUIDE, was developed that combines dosimetric information from the treatment planning system, patient and treatment characteristics, and established tumor control probability (TCP), and normal tissue complication probability (NTCP) models, to predict clinical outcome of radiotherapy treatment of LACC. Six Cox Proportional Hazards models based on data from 1341 patients of the EMBRACE-I study have been integrated. One TCP model for local tumor control, and five NTCP models for OAR morbidities. RESULTS: EviGUIDE incorporates TCP-NTCP graphs to help users visualize the clinical impact of different treatment plans and provides feedback on achievable doses based on a large reference population. It enables holistic assessment of the interplay between multiple clinical endpoints and tumour and treatment variables. Retrospective analysis of 45 patients treated with MR-IGABT showed that there exists a sub-cohort of patients (20%) with increased risk factors, that could greatly benefit from the quantitative and visual feedback. CONCLUSION: A novel digital concept was developed that can enhance clinical decision- making and facilitate personalized treatment. It serves as a proof of concept for a new generation of decision support systems in radiation oncology, which incorporate outcome models and high-quality reference data, and aids the dissemination of evidence-based knowledge about optimal treatment and serve as a blueprint for other sites in radiation oncology

Tools for large-scale data analytics of an international multi-center study in radiation oncology for cervical cancer

PURPOSE: To develop and implement a software that enables centers, treating patients with state-of-the-art radiation oncology, to compare their patient, treatment, and outcome data to a reference cohort, and to assess the quality of their treatment approach. MATERIALS AND METHODS: A comprehensive data dashboard was designed, which al- lowed holistic assessment of institutional treatment approaches. The software was tested in the ongoing EMBRACE-II study for locally advanced cervical cancer. The tool created individualized dashboards and automatic analysis scripts, verified pro- tocol compliance and checked data for inconsistencies. Identified quality assurance (QA) events were analysed. A survey among users was conducted to assess usability. RESULTS: The survey indicated favourable feedback to the prototype and highlighted its value for internal monitoring. Overall, 2302 QA events were identified (0.4% of all collected data). 54% were due to missing or incomplete data, and 46% originated from other causes. At least one QA event was found in 519/1001 (52%) of patients. QA events related to primary study endpoints were found in 16% of patients. Sta- tistical methods demonstrated good performance in detecting anomalies, with precisions ranging from 71% to 100%. Most frequent QA event categories were Treatment Technique (27%), Patient Characteristics (22%), Dose Reporting (17%), Outcome 156 (15%), Outliers (12%), and RT Structures (8%). CONCLUSION: A software tool was developed and tested within a clinical trial in radia- tion oncology. It enabled the quantitative and qualitative comparison of institutional patient and treatment parameters with a large multi-center reference cohort. We demonstrated the value of using statistical methods to automatically detect implau- sible data points and highlighted common pitfalls and uncertainties in radiotherapy for cervical cancer

Posttraumatic stress disorder after high dose rate brachytherapy for cervical cancer with two fractions in one application under spinal/epidural anesthesia : Incidence and risk factors

Purpose/Objectives: Purpose: To investigate the psychological consequences of high dose rate brachytherapy (BT) with two fractions in one application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Primary objective: To evaluate patients' traumatization in association with this BT procedure, in particular the incidence of acute and posttraumatic stress disorder (ASD/PTSD) with symptoms of intrusion, avoidance and hyperarousal. Secondary objectives: to evaluate the physical and psychological functioning before, during and after treatment; to identify pre-treatment risk factors for the development of PTSD symptoms and to assess qualitatively specific helpful experiences and stressful factors during the brachytherapy procedure. Material/Methods: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of ASD/PTSD (IES-R), anxiety/depression (HADS-D), quality of life (EORTC-QLQ-C30+CX24), physical functioning (WHO performance status) and pain (VAS); prior to and during treatment, one week and three months after treatment. Qualitative patients' interviews were recorded in open format for content analysis. Results: ASD occurred in 30% of patients one week, PTSD in 41% three months after treatment in association with this specific BT procedure. The time being bedbound between fractions was reported in 61% of patients to be stressful. Several impairments in physical and psychological functioning were found prior to, during and after treatment with different pattern of progress over time. Patients at risk for PTSD can be predicted pre-treatment with 82% accuracy. Helpful experiences were the support of the treatment team, psychological support and a positive attitude. Stressful factors were pain, organizational problems during treatment and immobility between brachytherapy fractions. Conclusions: The specific BT procedure, as performed in the investigated mono-institutional setting with 2 fractions in one application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the BT application itself, but the maintenance of the applicator under epidural anesthesia in the time between fractions. The results of physical and psychological functioning over time support a comprehensive counseling of patients in order to organize their professional and social life. Patients at risk for the development of PTSD may be identified prior to treatment in order to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful factors serve as basis for improvement of patient management, especially regarding pain control.Hintergrund: In der vorliegenden Arbeit werden die psychischen Auswirkungen der HDR Brachytherapie (BT) mit zwei Fraktionen innerhalb einer Applikation unter Anwendung von spinaler/epiduraler Anästhesie bei Patientinnen mit lokal fortgeschrittenem Zervixkarzinom untersucht. Hauptziel: Die Untersuchung von Traumatisierung der Patientinnen in Assoziation mit dieser Art der BT Anwendung, konkret die Inzidenz akuter und posttraumatischer Belastungsstörung (ASD/PTSD) mit Symptomen von Intrusion, Vermeidungsverhalten und vegetativer Übererregtheit. Nebenziele: Die Untersuchung körperlicher und psychischer Beeinträchtigungen vor, während und nach der Therapie, sowie die Identifizierung von Risikofaktoren für die Entstehung von PTSD bereits vor Therapiebeginn und die Darstellung von qualitativen Patientinnenberichten zu hilfreichen Erfahrungen und belastenden Faktoren. Material/Methode: In 50 lokal fortgeschrittenen Zervixkarzinompatientinnen wurden prospektiv anhand validierter Fragebögen folgende Faktoren vor Therapiebeginn, während der Therapie, sowie eine Woche und drei Monate nach Therapieende erhoben: ASD/PTSD (IES-R), Ängstlichkeit/Depressivität (HADS-D), Lebensqualität (EORTC-QLQ-C30+CX24), körperliches Funktionsniveau (WHO Status) und Schmerz (VAS). Qualitative Befragungen wurden in offenem Format für eine Inhaltsanalyse festgehalten. Ergebnisse: ASD in Assoziation mit der spezifischen Art der BT Anwendung trat in 30% der Patientinnen eine Woche nach Therapieende auf; PTSD in 41% drei Monate nach Therapieende. Die Liegezeit mit Applikator zwischen zwei Fraktionen wurde von 61% der Patientinnen als belastend erlebt. Verschiedene körperliche und psychische Beeinträchtigungen wurden vor, während und nach der Therapie festgestellt, mit jeweils unterschiedlichen Zeitverläufen. Risikopatientinnen für die Entwicklung einer PTSD können vor Therapiebeginn mit 82% Treffsicherheit vorhergesagt werden. Hilfreiche Erfahrungen umfaßten die Unterstützung vom Behandlungsteam, psychologische Unterstützung sowie eine positive Grundeinstellung. Belastende Faktoren stellten Schmerzen dar sowie organisatorische Probleme und Immobilität zwischen den BT Fraktionen. Schlußfolgerung: Die spezifische Art der BT Anwendung in der untersuchten Institution mit zwei Fraktionen innerhalb einer Applikation unter spinaler/epiduraler Anästhesie birgt ein beträchtliches Risiko einer Traumatisierung. Die Ursache scheint dabei nicht die Applikation an sich zu sein, sondern die Liegezeit mit Applikator zwischen den Fraktionen. Risikopatientinnen können bereits vor Therapiebeginn identifiziert werden, um gezielte psychologische Unterstützung anzubieten. Die Ergebnisse der körperlichen und psychischen Funktionsbeeinträchtigungen vor, während und nach der Therapie erleichtern eine umfassende Beratung von Patientinnen hinsichtlich der Organisation ihres Berufs- und Privatlebens. Die qualitativen Berichte der Patientinnen zu ihren hilfreichen Erfahrungen während der Brachytherapie sind eine ermutigende Rückmeldung an das Behandlungsteam. Die Berichte zu spezifisch belastenden Faktoren helfen bei Verbesserungsmaßnahmen im Patientenmanagement, vor allem hinsichtlich der Schmerzkontrolle.submitted by Kathrin KirchheinerAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheInt J Radiat Oncol Biol Phys. 2014 Apr 7. pii: S0360-3016(14)00203-X. doi: 10.1016/j.ijrobp.2014.02.018. [Epub ahead of print]Wien, Med. Univ., Diss., 2014OeBB(VLID)171473

Three or less? Decision making for or against selective reduction and psychological outcome in forty women with a triplet pregnancy

Objectives The aim of the study was to investigate decision making for or against multifetal pregnancy reduction (MFPR) and psychological outcome in women with a triplet pregnancy. Methods We investigated medical and sociodemographic variables and characteristics of the decision process for or against MFPR in forty women with triplet pregnancies who had either undergone MFPR (MFPR-group: N = 10) or had delivered triplets (triplet-group: N = 30). Moreover, emotional experiences of the reduction procedure were assessed. Psychological outcome was measured using the Beck Depression inventory (BDI) and the 36-Item Short Form Health Survey (SF-36). Results Women of the MFPR-group had a higher gestational age at delivery (p = 0.001), shorter NICU stay (p = 0.001), higher educational level (p = 0.010), more frequently utilized psychological counseling during the decision process (p = 0.016), rated their gynecologist as more helpful for the decision (p = 0.045), required more time for their decision (p = 0.016), and were more likely to be in paid employment at follow-up (p = 0.041) than women of the triplet-group. MFPR was experienced as stressful (90%) or terrifying (10%). At 3.2 (±2.2) years after delivery, the vast majority of women in both groups were free from clinically relevant depression. Conclusions MFPR, though associated with emotional distress related to the procedure, results in a satisfactory psychological outcome in the majority of women. The decision for or against MFPR may be related to sociodemographic (such as educational) variables, which further supports the concept of framing in medical decision making. Having triplets most probably is associated with multiple (e.g. social or economic) consequences that may remain poorly investigated

Co-occurrence of symptoms after radiochemotherapy in locally advanced cervix cancer patients:a cluster analysis

Background: State of the art combined radiochemotherapy and image-guided brachytherapy for locally advanced cervical cancer (LACC) has shown improved disease control and survival as well as a significant reduction of organ related morbidity. However, LACC cancer survivors are still experiencing a spectrum of symptoms. The aim of this study was to identify co-occurring symptoms in cervix cancer survivors by using patient-reported outcome and physician assessed morbidity. Materials and method: EMBRACE I is a multicenter prospective observational study with 1416 LACC patients (2008–2015). Information on physician-assessed morbidity and patient-reported outcome was assessed at baseline and at regular follow-ups up with the CTCAE v.3 and EORTC-C30/CX24, respectively. Patients with at least 2 years of follow-up were included and data from 3 months to 2 years was used in the analysis. Factor analysis was used on both EORTC and CTCAE data with symptoms and follow-ups as observations. The extracted factors represent clusters of symptoms. Subsequently, regression models were built to investigate associations between the symptom clusters and QOL. Results: The analysis included 742 patients. Despite the differences in the definition of physician-assessed and patient-reported symptoms, similar clusters are identified by the two assessment methods. Three main organ-related clusters are recognized for urinary, gastro-intestinal and vaginal morbidity. Furthermore, a general symptoms cluster where fatigue, pain, insomnia, neuropathy, and hot flashes have large weights is found. Lastly, a cluster with nausea, vomit and lack of appetite is also identified. The general, gastrointestinal and nausea clusters show significant associations with general QOL.Conclusions: This analysis on both PRO and physician-assessed morbidity found a cluster associated with general symptoms and organ-related symptom clusters (urinary, gastrointestinal, vaginal). This shows that LACC survivors experience a variety of co-occurring symptoms. Our analysis also shows that the cluster of general symptoms is associated with a decrease in QOL.</p

Co-occurrence of symptoms after radiochemotherapy in locally advanced cervix cancer patients: a cluster analysis

BACKGROUND: State of the art combined radiochemotherapy and image-guided brachytherapy for locally advanced cervical cancer (LACC) has shown improved disease control and survival as well as a significant reduction of organ related morbidity. However, LACC cancer survivors are still experiencing a spectrum of symptoms. The aim of this study was to identify co-occurring symptoms in cervix cancer survivors by using patient-reported outcome and physician assessed morbidity. MATERIALS AND METHOD: EMBRACE I is a multicenter prospective observational study with 1416 LACC patients (2008-2015). Information on physician-assessed morbidity and patient-reported outcome was assessed at baseline and at regular follow-ups up with the CTCAE v.3 and EORTC-C30/CX24, respectively. Patients with at least 2 years of follow-up were included and data from 3 months to 2 years was used in the analysis. Factor analysis was used on both EORTC and CTCAE data with symptoms and follow-ups as observations. The extracted factors represent clusters of symptoms. Subsequently, regression models were built to investigate associations between the symptom clusters and QOL. RESULTS: The analysis included 742 patients. Despite the differences in the definition of physician-assessed and patient-reported symptoms, similar clusters are identified by the two assessment methods. Three main organ-related clusters are recognized for urinary, gastro-intestinal and vaginal morbidity. Furthermore, a general symptoms cluster where fatigue, pain, insomnia, neuropathy, and hot flashes have large weights is found. Lastly, a cluster with nausea, vomit and lack of appetite is also identified. The general, gastrointestinal and nausea clusters show significant associations with general QOL. CONCLUSIONS: This analysis on both PRO and physician-assessed morbidity found a cluster associated with general symptoms and organ-related symptom clusters (urinary, gastrointestinal, vaginal). This shows that LACC survivors experience a variety of co-occurring symptoms. Our analysis also shows that the cluster of general symptoms is associated with a decrease in QOL

Characterization of a Functional Promoter Polymorphism of the Human Tryptophan Hydroxylase 2 Gene in Serotonergic Raphe Neurons.

Background Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin (5-HT) biosynthesis. Although dysfunction of 5-HT neurotransmission has been implicated in a variety of neuropsychiatric conditions, the human TPH2 promoter has not been characterized in vitro. Methods The functional relevance of TPH2 promoter polymorphisms was determined with luciferase assays in primary serotonergic neurons from rat raphe nuclei and in human small cell lung carcinoma cells (SHP-77 cells). We also investigated transcription factor binding to the variant promoter sequence with electrophoretic mobility shift assay (EMSA). Results The polymorphism rs11178997 of the human TPH2 promoter significantly reduced TPH2 transcriptional activity by 22% and 7% in primary serotonergic neurons and in SHP-77 cells, respectively. In contrast, no significant differences in promoter activity were observed for the G- and T-alleles of rs4570625. The EMSA revealed reduced binding of the transcription factor POU3F2 (also known as Brn-2, N-Oct-3) to the A-allele of the polymorphism rs11178997. Overexpression of POU3F2 resulted in a robust activation of the TPH2 promoter (2.7-fold). Conclusions Our data suggest that the human TPH2 promoter polymorphism rs11178997 impacts on gene expression, which might have implications for the development and function of the serotonergic system in the brain

Wiener klinische Wochenschrift / Migrate your mind: the role of palliative care in transcultural cancer treatment : A qualitative analysis

Background In increasingly multi-ethnic societies fostering cultural awareness and integration of immigrants is not only a political duty but also an obligation for social and healthcare systems. Importantly, cultural beliefs and needs strongly impact on the quality of life of cancer patients and may become even more crucial at the end of life. However, to date, ethnic and cultural aspects of palliative care are insufficiently researched. Methods This qualitative study at the Medical University of Vienna included 21 staff members from different disciplines in oncology and palliative care working with patients with various cultural backgrounds at the end of life. Semi-structured interviews were performed to gain insights into specific aspects of palliative care that are important in the clinical encounter with terminally ill cancer patients with migrant backgrounds and their relatives. Results Interviews revealed specific aspects of palliative care, which fell into four fundamental categories and were all perceived as beneficial in the clinical encounter with migrant clients: (A) structural and (B) personal conditions of the palliative care setting, (C) specific care and treatment intentions and (D) personnel requirements and attitudes. Conclusion This study revealed first insights into possibilities and prospects of transcultural palliative care for migrants and their relatives. The results might have important implications for the end of life care in this growing population.(VLID)509315