Hans-Henning Flechtner | Otto-von-Guericke-Universität Magdeburg (original) (raw)
Papers by Hans-Henning Flechtner
Journal of the National Cancer Institute, 2016
The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes ... more The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers. The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided. Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue (P < .001), vomit...
JNCI: Journal of the National Cancer Institute, 2011
Physicians use the Common Terminology Criteria for Adverse Events (CTCAE), as defined by the US N... more Physicians use the Common Terminology Criteria for Adverse Events (CTCAE), as defined by the US National Cancer Institute (NCI), as a standard classification system for reporting adverse events in cancer clinical trials (1). An adverse event is defined as an unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medical treatment or procedure; adverse events can include abnormal laboratory findings. Developed initially in 1982 by the NCI's Cancer Therapy Evaluation Program, this rating system is currently in its fourth version. The rapid pace of revisions reflects the changing needs of investigators for usable adverse events criteria and the increasing complexity of cancer clinical trials. In version 4 of the NCI-CTCAE, there are 790 specific items, with approximately 10% of the adverse events representing symptoms such as fatigue, pain, and nausea. Recently, it has become common practice in major American and European adult cancer clinical trial cooperative group studies to use patient-reported assessments of adverse events alongside clinician-reported assessments (2-4). This trend reflects the increasing importance of the patient's voice in cancer treatment, especially because studies (5-7) have shown that patient-reported outcomes can improve the accuracy and efficiency of symptomatic adverse event data collection. Several articles (8-10) have reported that clinician-reported assessments of symptoms tend to underestimate, or in some cases overestimate, the symptom burden compared with patient ratings
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie
Nature Reviews Disease Primers
In this article ref. 61 was incorrect and should have been 'Greaves, P. et al. Defining character... more In this article ref. 61 was incorrect and should have been 'Greaves, P. et al. Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells. Blood 122 (16), 2856-2863 (2013)'. The original article has been corrected.
European Journal of Haematology
Journal of Clinical Oncology
PURPOSE Many important details of health-related quality of life (HRQoL) after diagnosis and trea... more PURPOSE Many important details of health-related quality of life (HRQoL) after diagnosis and treatment of Hodgkin lymphoma (HL) are still unknown because large longitudinal studies of HRQoL are rare. Therefore, we analyzed a systematically assessed, comprehensive range of HRQoL domains in patients with HL of all stages from diagnosis up to 5 years of survivorship. PATIENTS AND METHODS We included patients with HL age 18-60 years at diagnosis from the German Hodgkin Study Group trials HD13, HD14, and HD15. We analyzed HRQoL using all functional and symptom scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 including deviations from reference values. We estimated the effect of different disease, patient, and treatment characteristics using multiple regression and repeated measures analysis and computed correlations of HRQoL scores. RESULTS We analyzed 4,215 patients with any HRQoL assessment within 5 years after treatment. Higher...
Frontiers in Human Neuroscience
Blood
Purpose: Hodgkin Lymphoma (HL) is one of the best curable cancers in adults. Thus, current resear... more Purpose: Hodgkin Lymphoma (HL) is one of the best curable cancers in adults. Thus, current research is focusing on the increasing proportion of HL survivors with respect to the long-term consequences of therapy. Especially health related quality of life (QoL) needs thorough investigation since this is relevant for HL patients, complex and so far there is limited knowledge. QoL incorporates different aspects such as general QoL, fatigue, emotional, physical, role, social, sexual and cognitive functions. This analysis is focusing on QoL in the HD10–12 trials of the GHSG with special emphasis on cognitive functions (CF) and possible predictors in a 2 year follow-up. Methods: Patients of the GHSG trials HD10–12 completed the QLQ-C30, the MFI20 and some additional items at the time of diagnosis, after chemotherapy, after radiotherapy and at follow-up examinations. We describe the courses of the QLQ-C30 scales with means and 95%-confidence intervals for each measurement point and in relat...
The Journal of Neuroscience
Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADH... more Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADHD), one of the most common psychiatric disorders in children and adolescents. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but the link between OFC dysfunction and behavioral deficits in ADHD, particularly in adolescence, remains poorly understood. Here we used advanced high-resolution functional magnetic resonance imaging (fMRI) of the human OFC in adolescents with ADHD and typically developing (TD) controls (N ϭ 39, age 12-16, all male except for one female per group) to study reward-related OFC responses and how they relate to behavioral dysfunction in ADHD. During fMRI data acquisition, participants performed a simple decision-making task, allowing us to image expectation-related responses to small and large monetary outcomes. Across all participants, we observed significant signal increases to large versus small expected rewards in the OFC. These responses were significantly enhanced in ADHD relative to TD participants. Moreover, stronger reward-related activity was correlated with individual differences in hyperactive/impulsive symptoms in the ADHD group, whereas high cognitive ability was associated with normalized OFC responses. These results provide evidence for the importance of OFC dysfunctions in the neuropathology of ADHD, highlighting the role of OFC-dependent goal-directed control mechanisms in this disorder.
Blood
935 Background: Long term impairment of quality of life (QoL) and elevated fatigue levels in Hodg... more 935 Background: Long term impairment of quality of life (QoL) and elevated fatigue levels in Hodgkin Lymphoma (HL) survivors have been reported. However, few longitudinal data and no conclusive knowledge on components and determinants of QoL exist so far. Therefore, the German Hodgkin Study Group (GHSG) assessed the patients` QoL within the prospectively randomized studies HD10-12 for a detailed longitudinal evaluation of QoL and fatigue. Methods: QoL was assessed with a psychometrically proven questionnaire (QLQ-S) which contains the EORTC QLQ-C30 among other scales and items. Patients answered the questionnaires before, during, and at the end of therapy and at regular follow-up visits. For all QLQ-C30 functional scales and fatigue, longitudinal courses up to 27 months from diagnosis are given with means and 95%-confidence intervals. Reference values from a German control population were used for interpretation of the results. Components and determinants of QoL were analyzed with s...
Blood
896 Purpose: Current research in HL is focusing on long-term consequences of therapy. Among these... more 896 Purpose: Current research in HL is focusing on long-term consequences of therapy. Among these, especially health related quality of life (HRQoL) needs thorough investigation since it becomes increasingly important for HL survivors. HRQoL is complex and incorporates different aspects such as general QoL, fatigue, emotional, physical, role, social, cognitive, and sexual functions. In this analysis, we focus on sexual functions (SX) in the HD10-12 trials of the GHSG and the influence of stage, treatment modality, social relationships (SF), and fatigue (FA). Methods: Between 1998 and 2002, the GHSG has conducted the fourth generation of clinical trials for the treatment of early favourable, early unfavourable and advanced stage HL (HD 10-12) involving a total of 4610 patients. Patients completed the QLQ-C30, the MFI20 and additional items for SX at the time of diagnosis, after chemotherapy, after radiotherapy, and at follow-up examinations. We describe SX with means and 95%-CI for e...
Kindheit und Entwicklung
Zusammenfassung. Vor dem Hintergrund der komplexen Wechselwirkung zwischen der Entstehung und Auf... more Zusammenfassung. Vor dem Hintergrund der komplexen Wechselwirkung zwischen der Entstehung und Aufrechterhaltung psychischer Störungen im Kindesalter einerseits und familiären Kontextbedingungen andererseits, bieten Eltern-Kind-Stationen die vielversprechende Möglichkeit das familiäre Umfeld intensiv in die kinderpsychiatrische Behandlung mit einzubeziehen. Um die Wirksamkeit dieser speziellen Therapieform zu untersuchen, wurden im Rahmen einer monozentrischen Fragebogenstudie unter klinischen Routinebedingungen im Ein-Gruppen-Prä-Post-Design anhand einer Stichprobe von 60 Familien die kindliche Symptombelastung (CBCL) und das elterliche Stresserleben (ESF) zu drei Zeitpunkten (Diagnostikblock, Beginn Therapieblock, Therapieende) erhoben. Während sich in der Wartezeit bis Therapiebeginn keine bedeutsamen Veränderungen zeigten, reduzierten sich im Verlauf der Behandlung sowohl die kindlichen Verhaltensauffälligkeiten als auch das elterliche Stresserleben signifikant. Damit liefern die...
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie
European Journal of Cancer
Introduction: Health-related quality of life (HRQOL) is increasingly recognised as an important e... more Introduction: Health-related quality of life (HRQOL) is increasingly recognised as an important end-point in cancer clinical trials. The concept of minimally important difference (MID) enables interpreting differences and changes in HRQOL scores in terms of clinical meaningfulness. We aimed to estimate MIDs for interpreting group-level change of European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30) scores in patients with malignant melanoma. Methods: Data were pooled from three published melanoma phase III trials. Anchors relying on clinician's ratings, e.g. performance status, were selected using correlation strength and
The Lancet Oncology
This is a repository copy of Statistical analysis of patient-reported outcome data in randomised ... more This is a repository copy of Statistical analysis of patient-reported outcome data in randomised controlled trials of locally advanced and metastatic breast cancer: a systematic review.
BMJ open, Jan 10, 2018
As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has inc... more As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated. Data will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for diffe...
Praxis der Kinderpsychologie und Kinderpsychiatrie, 2016
The Therapy Process of Accompanying Mothers in Multiple Family Therapy Groups: Evidence from a Ge... more The Therapy Process of Accompanying Mothers in Multiple Family Therapy Groups: Evidence from a German Child Psychiatric Setting This study provides an empirical contribution to the understanding of parents that accompany their children in psychiatric multiple family therapy settings (MFT). To this end, we conducted qualitative interviews with mothers that had successfully participated, with their diagnosed children (ages 3 to 9), in disorder-independent, age-homogeneous, and open family groups (the "Magdeburg Model") for several months. We performed a theoretical coding approach to the extensive interview material (n = 6 interviews, duration = 70 to 100 minutes each) according to Grounded Theory and extracted seven main and 29 sub-categories. These categories yield a coherent, complete, and specific subjective therapy model for this setting. One of the central findings is a profound understanding of to what extent and by which means the family group as a social arena paves...
Journal of the National Cancer Institute, 2016
The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes ... more The European Organisation for Research and Treatment of Cancer (EORTC) Patient-Reported Outcomes and Behavioural Evidence (PROBE) initiative was established to investigate critical topics to better understand health-related quality of life (HRQOL) of cancer patients and to educate clinicians, policy makers, and healthcare providers. The aim of this paper is to review the major research outcomes of the pooled analysis of HRQOL data along with the clinical data. We identified 30 pooled EORTC randomized controlled trials (RCTs), 18 NCIC-Clinical Trials Group RCTs, and two German Ovarian Cancer Study Group RCTs, all using the EORTC QLQ-C30. All statistical tests were two-sided. Evidence was found that HRQOL data can offer prognostic information beyond clinical measures and improve prognostic accuracy in cancer RCTs (by 5.9%-8.3%). Moreover, models that considered both patient- and clinician-reported scores gained more prognostic overall survival accuracy for fatigue (P < .001), vomit...
JNCI: Journal of the National Cancer Institute, 2011
Physicians use the Common Terminology Criteria for Adverse Events (CTCAE), as defined by the US N... more Physicians use the Common Terminology Criteria for Adverse Events (CTCAE), as defined by the US National Cancer Institute (NCI), as a standard classification system for reporting adverse events in cancer clinical trials (1). An adverse event is defined as an unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medical treatment or procedure; adverse events can include abnormal laboratory findings. Developed initially in 1982 by the NCI's Cancer Therapy Evaluation Program, this rating system is currently in its fourth version. The rapid pace of revisions reflects the changing needs of investigators for usable adverse events criteria and the increasing complexity of cancer clinical trials. In version 4 of the NCI-CTCAE, there are 790 specific items, with approximately 10% of the adverse events representing symptoms such as fatigue, pain, and nausea. Recently, it has become common practice in major American and European adult cancer clinical trial cooperative group studies to use patient-reported assessments of adverse events alongside clinician-reported assessments (2-4). This trend reflects the increasing importance of the patient's voice in cancer treatment, especially because studies (5-7) have shown that patient-reported outcomes can improve the accuracy and efficiency of symptomatic adverse event data collection. Several articles (8-10) have reported that clinician-reported assessments of symptoms tend to underestimate, or in some cases overestimate, the symptom burden compared with patient ratings
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie
Nature Reviews Disease Primers
In this article ref. 61 was incorrect and should have been 'Greaves, P. et al. Defining character... more In this article ref. 61 was incorrect and should have been 'Greaves, P. et al. Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells. Blood 122 (16), 2856-2863 (2013)'. The original article has been corrected.
European Journal of Haematology
Journal of Clinical Oncology
PURPOSE Many important details of health-related quality of life (HRQoL) after diagnosis and trea... more PURPOSE Many important details of health-related quality of life (HRQoL) after diagnosis and treatment of Hodgkin lymphoma (HL) are still unknown because large longitudinal studies of HRQoL are rare. Therefore, we analyzed a systematically assessed, comprehensive range of HRQoL domains in patients with HL of all stages from diagnosis up to 5 years of survivorship. PATIENTS AND METHODS We included patients with HL age 18-60 years at diagnosis from the German Hodgkin Study Group trials HD13, HD14, and HD15. We analyzed HRQoL using all functional and symptom scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 including deviations from reference values. We estimated the effect of different disease, patient, and treatment characteristics using multiple regression and repeated measures analysis and computed correlations of HRQoL scores. RESULTS We analyzed 4,215 patients with any HRQoL assessment within 5 years after treatment. Higher...
Frontiers in Human Neuroscience
Blood
Purpose: Hodgkin Lymphoma (HL) is one of the best curable cancers in adults. Thus, current resear... more Purpose: Hodgkin Lymphoma (HL) is one of the best curable cancers in adults. Thus, current research is focusing on the increasing proportion of HL survivors with respect to the long-term consequences of therapy. Especially health related quality of life (QoL) needs thorough investigation since this is relevant for HL patients, complex and so far there is limited knowledge. QoL incorporates different aspects such as general QoL, fatigue, emotional, physical, role, social, sexual and cognitive functions. This analysis is focusing on QoL in the HD10–12 trials of the GHSG with special emphasis on cognitive functions (CF) and possible predictors in a 2 year follow-up. Methods: Patients of the GHSG trials HD10–12 completed the QLQ-C30, the MFI20 and some additional items at the time of diagnosis, after chemotherapy, after radiotherapy and at follow-up examinations. We describe the courses of the QLQ-C30 scales with means and 95%-confidence intervals for each measurement point and in relat...
The Journal of Neuroscience
Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADH... more Alterations in motivated behavior are a hallmark of attention-deficit/hyperactivity disorder (ADHD), one of the most common psychiatric disorders in children and adolescents. The orbitofrontal cortex (OFC) plays a key role in controlling goal-directed behavior, but the link between OFC dysfunction and behavioral deficits in ADHD, particularly in adolescence, remains poorly understood. Here we used advanced high-resolution functional magnetic resonance imaging (fMRI) of the human OFC in adolescents with ADHD and typically developing (TD) controls (N ϭ 39, age 12-16, all male except for one female per group) to study reward-related OFC responses and how they relate to behavioral dysfunction in ADHD. During fMRI data acquisition, participants performed a simple decision-making task, allowing us to image expectation-related responses to small and large monetary outcomes. Across all participants, we observed significant signal increases to large versus small expected rewards in the OFC. These responses were significantly enhanced in ADHD relative to TD participants. Moreover, stronger reward-related activity was correlated with individual differences in hyperactive/impulsive symptoms in the ADHD group, whereas high cognitive ability was associated with normalized OFC responses. These results provide evidence for the importance of OFC dysfunctions in the neuropathology of ADHD, highlighting the role of OFC-dependent goal-directed control mechanisms in this disorder.
Blood
935 Background: Long term impairment of quality of life (QoL) and elevated fatigue levels in Hodg... more 935 Background: Long term impairment of quality of life (QoL) and elevated fatigue levels in Hodgkin Lymphoma (HL) survivors have been reported. However, few longitudinal data and no conclusive knowledge on components and determinants of QoL exist so far. Therefore, the German Hodgkin Study Group (GHSG) assessed the patients` QoL within the prospectively randomized studies HD10-12 for a detailed longitudinal evaluation of QoL and fatigue. Methods: QoL was assessed with a psychometrically proven questionnaire (QLQ-S) which contains the EORTC QLQ-C30 among other scales and items. Patients answered the questionnaires before, during, and at the end of therapy and at regular follow-up visits. For all QLQ-C30 functional scales and fatigue, longitudinal courses up to 27 months from diagnosis are given with means and 95%-confidence intervals. Reference values from a German control population were used for interpretation of the results. Components and determinants of QoL were analyzed with s...
Blood
896 Purpose: Current research in HL is focusing on long-term consequences of therapy. Among these... more 896 Purpose: Current research in HL is focusing on long-term consequences of therapy. Among these, especially health related quality of life (HRQoL) needs thorough investigation since it becomes increasingly important for HL survivors. HRQoL is complex and incorporates different aspects such as general QoL, fatigue, emotional, physical, role, social, cognitive, and sexual functions. In this analysis, we focus on sexual functions (SX) in the HD10-12 trials of the GHSG and the influence of stage, treatment modality, social relationships (SF), and fatigue (FA). Methods: Between 1998 and 2002, the GHSG has conducted the fourth generation of clinical trials for the treatment of early favourable, early unfavourable and advanced stage HL (HD 10-12) involving a total of 4610 patients. Patients completed the QLQ-C30, the MFI20 and additional items for SX at the time of diagnosis, after chemotherapy, after radiotherapy, and at follow-up examinations. We describe SX with means and 95%-CI for e...
Kindheit und Entwicklung
Zusammenfassung. Vor dem Hintergrund der komplexen Wechselwirkung zwischen der Entstehung und Auf... more Zusammenfassung. Vor dem Hintergrund der komplexen Wechselwirkung zwischen der Entstehung und Aufrechterhaltung psychischer Störungen im Kindesalter einerseits und familiären Kontextbedingungen andererseits, bieten Eltern-Kind-Stationen die vielversprechende Möglichkeit das familiäre Umfeld intensiv in die kinderpsychiatrische Behandlung mit einzubeziehen. Um die Wirksamkeit dieser speziellen Therapieform zu untersuchen, wurden im Rahmen einer monozentrischen Fragebogenstudie unter klinischen Routinebedingungen im Ein-Gruppen-Prä-Post-Design anhand einer Stichprobe von 60 Familien die kindliche Symptombelastung (CBCL) und das elterliche Stresserleben (ESF) zu drei Zeitpunkten (Diagnostikblock, Beginn Therapieblock, Therapieende) erhoben. Während sich in der Wartezeit bis Therapiebeginn keine bedeutsamen Veränderungen zeigten, reduzierten sich im Verlauf der Behandlung sowohl die kindlichen Verhaltensauffälligkeiten als auch das elterliche Stresserleben signifikant. Damit liefern die...
Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie
European Journal of Cancer
Introduction: Health-related quality of life (HRQOL) is increasingly recognised as an important e... more Introduction: Health-related quality of life (HRQOL) is increasingly recognised as an important end-point in cancer clinical trials. The concept of minimally important difference (MID) enables interpreting differences and changes in HRQOL scores in terms of clinical meaningfulness. We aimed to estimate MIDs for interpreting group-level change of European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30) scores in patients with malignant melanoma. Methods: Data were pooled from three published melanoma phase III trials. Anchors relying on clinician's ratings, e.g. performance status, were selected using correlation strength and
The Lancet Oncology
This is a repository copy of Statistical analysis of patient-reported outcome data in randomised ... more This is a repository copy of Statistical analysis of patient-reported outcome data in randomised controlled trials of locally advanced and metastatic breast cancer: a systematic review.
BMJ open, Jan 10, 2018
As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has inc... more As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated. Data will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for diffe...
Praxis der Kinderpsychologie und Kinderpsychiatrie, 2016
The Therapy Process of Accompanying Mothers in Multiple Family Therapy Groups: Evidence from a Ge... more The Therapy Process of Accompanying Mothers in Multiple Family Therapy Groups: Evidence from a German Child Psychiatric Setting This study provides an empirical contribution to the understanding of parents that accompany their children in psychiatric multiple family therapy settings (MFT). To this end, we conducted qualitative interviews with mothers that had successfully participated, with their diagnosed children (ages 3 to 9), in disorder-independent, age-homogeneous, and open family groups (the "Magdeburg Model") for several months. We performed a theoretical coding approach to the extensive interview material (n = 6 interviews, duration = 70 to 100 minutes each) according to Grounded Theory and extracted seven main and 29 sub-categories. These categories yield a coherent, complete, and specific subjective therapy model for this setting. One of the central findings is a profound understanding of to what extent and by which means the family group as a social arena paves...