Hans-Henning Flechtner

Fatigue in long-term survivors of Hodgkin‘s lymphoma; a report from the German Hodgkin Lymphoma Study Group (GHSG)

Although treatment regimens for Hodgkins lymphoma have become more sophisticated, little is known about the prevalence of fatigue in long-term survivors. Therefore, we investigated the fatigue status of long-term survivors of Hodgkins lymphoma and a control group using a pre-validated questionnaire. In 1995/1996, we contacted 1981 patients, who were enrolled in the German Hodgkin Studies HD 1-6. All patients were treated according to the treatment protocols HD1-3 (1981-1988) and HD 4-6 (1988-1993). The patients with a current status of complete remission were asked to complete a quality-of-life (QoL) questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ C-30)) and a fatigue questionnaire (Multidimensional Fatigue Inventory (MFI)). The results were compared with the data from 935 controls, matched for age, gender and living area. Eight-hundred and eighteen questionnaires from the patients were available for analysis. The median time between the end of treatment and completing the questionnaire is 5.2 years. Fatigue levels of patients with Hodgkins lymphoma are high, even years after treatment. Fatigue dimensions are significantly influenced by several clinical and non-clinical factors. Fatigue levels of Hodgkins lymphoma patients are significantly higher than those of the control group. Further investigations are warranted to explore the effectiveness of treatment strategies for fatigue.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients

BACKGROUND We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Epoetin Alfa in Patients With Advanced-Stage Hodgkin's Lymphoma: Results of the Randomized Placebo-Controlled GHSG HD15EPO Trial

PURPOSE To determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkins lymphoma (HL). PATIENTS AND METHODS The prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs. RESULTS PROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P < .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P < .001). CONCLUSION Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.

Altered evoked gamma-band responses reveal impaired early visual processing in ADHD children.

Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90ms after visual stimulation in human EEG, have been assigned a pivotal role in early visual processing. In particular, they are involved in memory matching processes and are enhanced when known stimuli are processed. The current study examined whether evoked GBR patterns during early memory matching processes could be indicative of an early visual processing deficit in ADHD patients. EEG was recorded from 13 young ADHD patients as well as 13 age-matched healthy participants. Both groups performed a simple forced choice reaction task employing line drawings of either known real-world items with representations in long-term memory or physically similar unknown items without such representations. Evoked GBRs of ADHD patients did not differentiate between known and unknown items. However, in healthy children, evoked GBRs were enhanced when stimuli matched a representation stored in memory. This finding indicates disadvantages at early visual processing stages in ADHD patients: In contrast to healthy participants, ADHD children lack an early memory based classification, possibly resulting in an impaired ability to rapidly reallocate attentional resources to relevant stimuli. These findings suggest that impaired early automatic stimulus classification in ADHD patients could be involved in deficits of selective and sustained attention.

Psychological distress in cancer patients with underage children: gender-specific differences.

Findings on gender differences in the psychological distress of cancer patients have been inconsistent. The objectives of the current study were to examine whether being a parent differentially modulates anxiety and depression in men and women and to compare whether psychological distress differs in male and female patients with and without children.

Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial

Background:Little is known about whether changes in health-related quality of life (HRQoL) scores from baseline during treatment also predict survival, which we aim to investigate in this study.Methods:We analysed data from 391 advanced non-small-cell lung cancer (NSCLC) patients enrolled in the EORTC 08975 study, which compared palliative chemotherapy regimens. HRQoL was assessed at baseline and after each chemotherapy cycle using the EORTC QLQ-C30 and QLQ-LC13. The prognostic significance of HRQoL scores at baseline and their changes over time was assessed with Cox regression, after adjusting for clinical and socio-demographic variables.Results:After controlling for covariates, every 10-point increase in baseline pain and dysphagia was associated with 11% and 12% increased risk of death with hazard ratios (HRs) of 1.11 and 1.12, respectively. Every 10-point improvement of physical function at baseline (HR=0.93) was associated with 7% lower risk of death. Every 10-point increase in pain (HR=1.08) was associated with 8% increased risk of death at cycle 1. Every 10-point increase in social function (HR=0.91) at cycle 2 was associated with 9% lower risk of death.Conclusions:Our findings suggest that changes in HRQoL scores from baseline during treatment, as measured on subscales of the EORTC QLQ-C30 and QLQ-LC13, are significant prognostic factors for survival.

Cancer-related fatigue in patients with and survivors of Hodgkin's lymphoma: a longitudinal study of the German Hodgkin Study Group

BACKGROUND Patients with Hodgkins lymphoma might have persistent fatigue even years after treatment. However, knowledge of the development of fatigue persisting long after completion of treatment is limited. Therefore, we did a detailed analysis of fatigue in our first-line clinical trials for early-stage favourable (HD13 trial), early-stage unfavourable (HD14 trial), and advanced-stage (HD15 trial) Hodgkins lymphoma. Beyond the description of fatigue from diagnosis up to 5 years after treatment, we aimed to assess any effect of patient characteristics, disease characteristics, or treatment characteristics on persistent fatigue. METHODS In this longitudinal study, we included patients with early-stage favourable, early-stage unfavourable, and advanced-stage Hodgkins lymphoma from the HD13, HD14, and HD15 trials, respectively, aged between 18 and 60 years. Eligible patients for these trials had newly diagnosed, histologically proven Hodgkins lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or lower, HIV negativity, and absence of comorbidity disallowing protocol treatment. We used the fatigue scale of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire to assess fatigue from diagnosis up to 5 years after the end of treatment. The primary outcomes of interest in this study were fatigue scores in the second and fifth year after end of treatment. We estimated the effect of different disease, patient, and treatment characteristics on fatigue with multiple regression analyses and identified fatigue trajectories with growth mixture models. The regression analyses and growth mixture models used robust and full information maximum likelihood estimates to account for missing data. The HD13, HD14, and HD15 trials are registered as international standard randomised controlled trials, ISRCTN63474366, ISRCTN04761296, and ISRCTN32443041, respectively. FINDINGS The HD13 trial enrolled patients with early-stage favourable disease from Jan 28, 2003, to Sept 30, 2009; the HD14 trial enrolled patients with early-stage unfavourable disease from Jan 28, 2003, to Dec 23, 2009; and the HD15 trial enrolled patients with advanced-stage disease from Jan 28, 2003, to April 18, 2008. 5306 patients were enrolled in these trials. We analysed 4215 patients with any valid fatigue assessment up to 5 years after the end of treatment. Patients with higher tumour burden at diagnosis had more fatigue at baseline (mean fatigue score in HD13: 30·8 [SD 28·0]; in HD14: 39·8 [29·4], and in HD15: 49·0 [30·2]). Fatigue scores (FA) in the second year after the end of treatment were 28·5 (24·7) in HD13, 28·8 (24·4) in HD14, and 30·7 (24·4) in HD15; in the fifth year after the end of treatment FA was 30·8 (26·0) in HD13, 27·1 (24·8) in HD14, and 28·2 (24·9) in HD15. Predictors of fatigue in the second and fifth year after end of treatment were baseline fatigue (p<0·0001) and age as a continuous variable (p<0·0001). In addition to preceding fatigue and age, patient sex and Hodgkins lymphoma specific risk factors at baseline did not consistently and significantly improve the prognosis of fatigue in the first, second, and fifth year after end of treatment. There was no significant effect of treatment on fatigue scores in the second and fifth year after treatment. INTERPRETATION Our findings show a high incidence of severe acute and persistent fatigue in Hodgkins lymphoma survivors, which is largely independent of tumour stage and treatment. Our results contribute to a better understanding of fatigue in patients with Hodgkins lymphoma and Hodgkins lymphoma survivors and could inform development of urgently needed intervention strategies. FUNDING Deutsche Krebshilfe.

Health-related quality of life in small-cell lung cancer: a systematic review on reporting of methods and clinical issues in randomised controlled trials

Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

Sexual quality of life in Hodgkin Lymphoma: a longitudinal analysis by the German Hodgkin Study Group.

Background:Health-related quality of life (HRQoL) comprises different domains of physical, mental, and social well-being. In this analysis, we focus on sexual quality of life in Hodgkin Lymphoma (HL) patients.Methods:Four-thousand one-hundred and sixty patients enroled in the HD10–HD12 trials underwent HRQoL assessment. Instruments included the Quality of Life Questionnaire for survivors (QLQ-S), combining the European Organisation for Research and Treatment of Cancer QLQ-C30, Multidimensional fatigue (FA) inventory (MFI-20) and an additional sexual functioning (SX) scale. We describe SX up to 27 months after therapy and analyse relationship to stage, age, gender, FA, social functioning, and therapy. Statistical methods range from descriptive statistics to a classification of SX courses, and a longitudinal structural equations model with full information maximum likelihood estimation of missing data. In the analysis, a score below 50 was used to describe severe sexual dysfunction.Results:Three-thousand two-hundred and eight patients provided data on SX. Patients in advanced stages reported lower SX than patients in early stages both, before and after the treatment. During follow-up, an improvement of SX compared with baseline was detected, except for those ⩾50 years. Patients in early stages reached normal SX, whereas advanced-stage patients remained below the reference value for healthy controls. Sexual functioning during follow-up was significantly and strongly related to previous SX, other HRQoL measures, age, and stage, and to lesser degree with gender and chemotherapy.Conclusion:Overall, HL patients have a decreased sexual quality of life at baseline, which improves after therapy and normalises in early-stage patients. Importantly, long-term SX is more closely related to patient characteristics and SX at baseline than to the intensity of treatment.

Children of cancer patients: Prevalence and predictors of emotional and behavioral problems

Children of patients with cancer are at increased risk for developing emotional and behavioral problems. This study explored the prevalence and predictors of emotional and behavioral problems in Children of cancer patients in a multisite research project.