Quality of life as subjective experience: Reframing of perception in patients with colon cancer undergoing radical resection with or without adjuvant chemotherapy

Purpose and background: We examined whether patients with colon cancer undergoing surgery with or without adjuvant chemotherapy change the internal standards on which they base their quality-of-life (QL) estimation, and, if they do so, whether this reframing alters interpretation of QL findings. These questions were addressed within a randomized clinical trial of the Swiss Group for Clinical Cancer Research (SAKK 40/93). Patients and methods: After radical resection of adenocar-cinoma of the colon (pT1-4pN>0M0 and pT3-4pN0M0) and perioperative chemotherapy, patients were randomized to three treatment arms: observation only (A), 5-FU 450 rag/m2plus Levamisol (B), or 5-FU 600 mg/m2 (C). QL was measured by linear analogue self-assessment indicators. Patients estimated their pre-surgery QL both before surgery and retrospectively thereafter, and their pre-adjuvant QL both at the beginning of randomly assigned chemotherapy or observation and retrospectively about two months later. Thereafter, current QL was assessed. Paired t-tests were used to test the hypotheses of no change. Results: Overall, 187 patients with at least one pair of corresponding questionnaires were analyzed. Patients estimated their pre-surgery QL after surgery significantly lower than before and their pre-adjuvant QL under treatment or observation also lower than at the beginning. In the adjuvant phase, in contradiction to our hypothesis, chemotherapy had almost no impact on these changes attributed to reframing. Conventionally assessed changes indicated an improvement in QL. Patients with treatment C reported less improvement in functional performance than those with B or those under observation (P = 0.04). Patients with treatment B indicated a greater worsening in nausea/vomiting than those with C, whereas patients with observation only showed an improvement (P = 0.0009). After adjustment of current QL scores under treatment or observation to patients' retrospective estimation, the treatment effects were diluted but the overall improvement was substantially amplified in most QL indicators. Conclusions: Patients with colon cancer substantially re-frame their perception in estimating QL both under radical resection and under adjuvant chemotherapy or observation. This effect is an integral part of patients' adaptation to disease and treatment. An understanding of this phenomenon is of particular relevance for patient care. Its role in evaluating QL endpoints in clinical trials needs further investigatio

Eight months of continuous positive airway pressure (CPAP) decrease tumor necrosis factor alpha (TNFA) in men with obstructive sleep apnea syndrome

Objectives: The aim of this study was to assess serum tumor necrosis factor alpha (TNFA) concentrations 8months of continuous positive airway pressure (CPAP) therapy. Design: This study used prospective, observational clinical trial. Patients: Sixty-six patients with newly diagnosed sleep apnea syndrome (12 women, 54 men), age 52.3 ± 9.8 (mean ± SD) with a body mass index of 29.7 ± 4.4 and an apnea-hypopnea index of 39.7 ± 26.8, were studied. Intervention: CPAP was administered for a mean of 7.8 ± 1.3months. Measurements and results: TNFA concentrations using an ultrasensitive ELISA assay at baseline and follow-up. TNFA decreased in men with high (5.2 ± 1.7h/night, −0.46 ± 1.1ng/l, p = 0.001) and with low (2.5 ± 1.0h/night −0.63 ± 0.77ng/l, p = 0.001) adherence but not in women. Average number of hours of CPAP use correlated positively with delta TNFA (R 2 0.08, p = 0.04) Conclusion: Long-term CPAP positively affects TNFA even in men with poor adherence to CPA

Clinical relevance of single item quality of life indicators in cancer clinical trials

We investigated the hypothesis that global single-item quality-of-life indicators are less precise for specific treatment effects (discriminant validity) than multi-item scales but similarly efficient for overall treatment comparisons and changes over time (responsiveness) because they reflect the summation of the individual meaning and importance of various factors. Linear analogue self-assessment (LASA) indicators for physical well-being, mood and coping were compared with the Hospital Anxiety and Depression Scale (HAD), the Mood Adjective Check List (MACL) and the emotional behaviour and social interaction scales of the Sickness Impact Profile (SIP) in 84 patients with early breast cancer receiving adjuvant therapy. Discriminant validity was investigated by multitrait-multimethod correlation, responsiveness by standardized response mean (SRM). Discriminant validity of the indicators was present at baseline but less under treatment. Responsiveness was demonstrated by the expected pattern among treatments (P = 0.008). In patients without chemotherapy, the SRMs indicated moderate (0.5–0.8) to large (>0.8) improvements in physical well-being (0.70), coping (0.92), HAD anxiety (0.89) and depression (1.19), and MACL mental well-being (0.68). In patients with chemotherapy for the first 3 months, small but clinically significant improvements (>).2) included mood (0.38), coping (0.41), HAD axiety (0.31) and MACL mental well-being (0.35). Patients with 6 months chemotherapy showed no changes. The indicators also reflected mood disorders (HAD) and marked psychosocial dysfunction (SIP) at baseline and under treatment according to pre-defined cut-off levels. Global indicators were confirmed to be efficient for evaluating treatments overall and changes over time. The lower reliability of single as opposed to multi-item scales affects primarily their discriminant validity. This is less decisive in large sample sizes. © 2001 Cancer Research Campaign http://www.bjcancer.co

N-terminal pro-B-type natriuretic peptide and functional capacity in patients with obstructive sleep apnea

The obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular abnormalities including left ventricular hypertrophy, left ventricular diastolic dysfunction, and endothelial dysfunction. The present study evaluated whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and peak oxygen consumption (peak VO2), both integral markers of cardiovascular function, are related to OSAS severity. In addition, we tested whether NT-proBNP levels depend on body composition in OSAS patients, similar to what has been reported in patients without OSAS. Eighty-nine patients with untreated OSAS underwent NT-proBNP measurement, dual X-ray absorptiometry, and cardiopulmonary exercise testing. In a representative subgroup (n = 32), transthoracic echocardiography was performed. The severity of OSAS was classified based on apnea-hypopnea index (AHI) values as mild (AHI 5-15h−1), moderate (AHI 15-30h−1), and severe (AHI >30h−1). OSAS was mild in 19 (21%), moderate in 21 (24%), and severe in 49 (55%) patients. NT-proBNP levels did not differ among patients with mild [30 (10-57)], moderate [37 (14-55)], and severe [24 (13-49) pg/ml; p = 0.8] OSAS and were not related to body mass index (r = 0.07; p = 0.5), percent lean body mass (r = −0.17; p = 0.1), and percent fat mass (r = 0.18; p = 0.1). Percent predicted peak VO2 was on average normal and did not differ among patients with mild (115 ± 26), moderate (112 ± 23), and severe OSAS (106 ± 29%; p = 0.4). Body weight-indexed peak VO2 did not differ among patients with mild (31.9 ± 10.3), moderate (32.1 ± 7.9), and severe OSAS (30.0 ± 9.9ml kg−1 min−1; p = 0.6) either. Lower NT-proBNP (β = −0.2; p = 0.02) was independently but weakly associated with higher body weight-indexed peak VO2. In the echocardiography subgroup, NT-proBNP was not significantly related to left ventricular mass index (r = 0.26; p = 0.2). In conclusion, NT-proBNP and peak VO2 are not related to OSAS severity, and NT-proBNP poorly reflects left ventricular hypertrophy in OSAS. The lack of a relationship between NT-proBNP and OSAS severity is not due to a significant influence of body composition on NT-proBNP. There is an association between higher NT-proBNP and lower peak VO2, indicating that NT-proBNP is a marker of cardiorespiratory fitness in patients with OSAS. However, the association is too weak to be clinically usefu

Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK).

The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients' quality of life (QL) during chemotherapy is addressed in the context of a randomised clinical trial comparing early and late alternating chemotherapy (SAKK protocol 15/84). The relative impact of initial tumour stage and performance status, previous weight loss, sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124-130 patients (according to available QL data) with more than 400 questionnaires. Fatigue/malaise, personal functioning, emotional and general well-being were prospectively selected as QL indicators. Predefined summary measures (average QL score over chemotherapy cycles, 'minimum', 'maximum' and 'final' improvement) were analysed separately by scale in various patient groups. General linear models adjusted for treatment arm and response were used to confirm the univariate findings. Within the overall sample, the average QL scores over six cycles were predicted by initial prognostic factors. Patients with poor prognostic factors reported worse QL. Within a limited sample (with baseline QL), patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment. Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors. The impact of initial prognostic factors was consistently confirmed in the three analyses. Levels of performance status and weight loss best discriminated QL. Initial tumour stage, performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy, even after controlling for response to treatment. Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome, especially in patients with extensive disease

Mandatory communication skills training for oncologists: enforcement does not substantially impact satisfaction

Purpose: Even though there is evidence that both patients and oncology clinicians are affected by the quality of communication and that communication skills can be effectively trained, so-called Communication Skills Trainings (CSTs) remain heterogeneously implemented. Methods: A systematic evaluation of the level of satisfaction of oncologists with the Swiss CST before (2000-2005) and after (2006-2012) it became mandatory. Results: Levels of satisfaction with the CST were high, and satisfaction of physicians participating on a voluntary or mandatory basis did not significantly differ for the majority of the items. Conclusions: The evaluation of physicians' satisfaction over the years and after introduction of mandatory training supports recommendations for generalized implementation of CST and mandatory training for medical oncologists

Intravenous immunoglobulin in the treatment of primary trigeminal neuralgia refractory to carbamazepine: a study protocol[ISRCTN33042138]

BACKGROUND: We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin (IVIG) in a prospective, open-label cohort study. A randomised, placebo controlled, double blinded study is needed to confirm these results. We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia (rpTN), as these had responded particularly well to IVIG. A protocol involving the use of IVIG in rpTN is complex for three reasons: 1. The effect of IVIG does not follow simple dose-response rules; 2. The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and >1 year; 3. TN is characterized by extremely severe pain, for which operative intervention is (if temporarily) helpful in most patients. DESIGN: A placebo controlled, parallel, add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study. Study groups are compared using Kaplan-Maier survival analysis. Patients record their response to treatment ("severe, moderate, slight, no pain"). The study coordinator monitors pain diaries. Severe or moderate pain of three days duration will result in termination of the study for that patient. CONCLUSIONS: This study design utilizes a method of survival analysis and is novel in chronic pain research. It allows for both early departure from the study and voluntary crossover upon non-response. It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, −2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy

Duration of adjuvant chemotherapy for breast cancer: a joint analysis of two randomised trials investigating three versus six courses of CMF

Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive ‘classical’ cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (±s.e.) were 54±2% for three cycles and 55±2% for six cycles (n=1024; risk ratio (risk ratio: CMF×3/CMF×6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation