The effects of illness beliefs and chemotherapy impact on quality of life in Japanese and Dutch patients with breast or lung cancer.

BACKGROUND: Responses to diagnosis and treatment of cancer are mediated by a patient's illness perceptions. Such perceptions, though different among individuals, may be culturally dependent, and act upon health related quality of life (HRQOL). Over time, individual patients show different types of response trajectories. Four issues were investigated: (I) country and disease differences in illness beliefs between Japanese and Dutch patients with lung or breast cancer; (II) country and disease differences in HRQOL in early chemotherapy; (III) individual, country, and disease differences among HRQOL trajectories; (IV) the impact of illness beliefs on HRQOL trajectories. METHODS: A total of 89 Japanese and Dutch patients with lung or breast cancer cooperated immediately before, one week after, and eight weeks after the start of chemotherapy. Data included the EORTC QLQ-C30 quality of life (QL) questionnaire and the Brief Illness Perception Questionnaire (B-IPQ). EORTC QLQ-C30 scales were summarized by two dimensions: generalized quality of life (GENQOL) and psychological well-being (PSYQOL). RESULTS: (I) Japanese patients had higher means on B-IPQ's concern and time line than Dutch patients. Japanese lung cancer patients had a higher mean on treatment control than all other patients; (II) no differences between country and cancer type occurred on the two HRQOL dimensions. First assessment HRQOL differed significantly from the second and third assessments without differences between the latter two. Between the first two assessments, a decrease in GENQOL occurred, together with an improvement in PSYQOL; (III) individual differences dominated the trajectories; (IV) negative beliefs usually coincided with lower scores on GENQOL and PSYQOL. Patients initially lower on PSYQOL generally showed larger improvement. CONCLUSIONS: Individual differences in HRQOL dominate differences between culture and cancer type, and illness beliefs influence HRQOL changes in individual patients. Clinical application is possible through influencing the patient's illness beliefs to create an optimal starting position for chemotherapy.

Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly.

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality.

Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly.

BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality.

Randomised study of tegafur-uracil plus leucovorin versus capecitabine as first-line therapy in elderly patients with advanced colorectal cancer--TLC study.

BACKGROUND: Prospective data on chemotherapy for (frail) elderly patients with advanced colorectal cancer (aCRC) are scant. UFT/leucovorin might be as effective as and less toxic than capecitabine. We firstly randomized both agents in patients >65 years with aCRC not amenable to receive combination chemotherapy. PATIENTS AND METHODS: Patients were randomised between first-line oral UFT/leucovorin and capecitabine in a Dutch multicentre trial. Primarily, efficacy and toxicity were determined. Secondary, quality of life (QoL) and abbreviated common geriatric assessment (aCGA) were analysed. RESULTS: Sixty-seven patients were randomised with a median age of 77 years and 96% being frail. After interim analysis it was decided to stop recruitment because of low accrual. At a median follow up of 34 months, the median progression-free survival (PFS) and overall survival (OS) were similar for both therapies, being 21 weeks (p=0.17) and 12 months (p=0.83), respectively. The overall response rates were 24% and 21%, respectively. Two patients died of possible treatment related complications in the UFT/leucovorin arm and 3 patients in the capecitabine arm. For UFT/leucovorin significantly less grade 3 or 4 hand/foot syndrome (0 vs 5) was observed. Overall, PFS was related to Charlson-comorbidity index (p=0.049), LDH (p=0.0011) and albumin (p=0.009). OS was related to LDH (p=0.0003), albumin (p=0.0001), QoLC30/CR38 (p=0.041), QoL visual analogue scale (VAS; p=0.016), and GFI (p=0.028). CONCLUSION: UFT/leucovorin and capecitabine had similar efficacy and different toxicity profiles in frail elderly patients with aCRC. Baseline serum levels of albumin and LDH, Charlson-comorbidity index, GFI and QoL were prognostic for clinical outcome.

Summarizing the fifteen scales of the EORTC QLQ-C30 questionnaire by five aggregate scales with two underlying dimensions: a literature review and an empirical study.

The intercorrelations among the 15 scales of the 30-item Core version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire suggest that one may combine (1) the physical functioning and role functioning scales, (2) the emotional functioning and cognitive functioning scales, and (3) the nine symptom scales. Together with the global health/quality of life scale and the social functioning scale, five measures remain. Principal component analysis of those five measures, using data from Japanese and Dutch breast and lung cancer patients, yielded two dimensions: (1) generalized health related quality of life and (2) health-independent psychological well-being. The correlations of these dimensions with the Brief Illness Perception Questionnaire and Karnofsky performance substantiated this interpretation.

Physical activity and survival of postmenopausal, hormone receptor-positive breast cancer patients: results of the Tamoxifen Exemestane Adjuvant Multicenter Lifestyle study.

BACKGROUND: Physical activity has been related to improved breast cancer outcomes. Especially in the older breast cancer population, physical activity may be important because old age is associated with comorbidities and decreased physical function. The purpose of this study was to investigate the relation between physical activity and overall survival, breast cancer-specific survival, and recurrence in several age groups of postmenopausal breast cancer patients. METHODS: The Tamoxifen Exemestane Adjuvant Multinational Lifestyle study was a side study of the Tamoxifen Exemestane Adjuvant Multinational trial and prospectively investigated lifestyle habits of postmenopausal, hormone receptor-positive breast cancer patients. The relations between prediagnosis and postdiagnosis physical activity and overall survival, breast cancer-specific survival, and recurrence-free survival were assessed with Cox regression and competing risk regression models. RESULTS: Among 521 patients, high levels of physical activity before and after the diagnosis were associated with better overall survival (the multivariate hazard ratios were 0.50 [95% confidence interval = 0.26-0.98] and 0.57 (95% confidence interval = 0.26-1.40] for patients who were very active before and after the diagnosis, respectively, in comparison with inactive patients). This was most evident in patients who were 65 years old or older. Physical activity was not significantly associated with breast cancer-specific survival or the relapse-free period. CONCLUSIONS: Overall survival was better for patients who were active before and after the diagnosis. In contrast with previous studies, breast cancer survival and the risk of recurrence were not significantly associated with physical activity. These findings confirmed the need for more studies investigating the use of physical activity to supplement breast cancer treatment in older patients.

Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.

PURPOSE: Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis. METHODS: Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented. RESULTS: The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented. CONCLUSION: We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia.

PURPOSE: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. PATIENTS AND METHODS: In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. RESULTS: After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). CONCLUSION: In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.

Illness perceptions and quality of life in Japanese and Dutch women with breast cancer.

Knowledge on cross-cultural quality of life (QOL) and illness perceptions may help women with breast cancer cope more effectively. The self regulation model (SRM) guided the current exploratory longitudinal pilot-study. Central to SRM is the perception of health threats and their effects on QOL. Illness perceptions and QOL were assessed in 22 Dutch and 21 Japanese patients with breast cancer who filled out questionnaires before, 1 week, and 8 weeks after the first chemotherapy course. The questionnaires assessed QOL and illness perceptions. Patients' scores were compared with groups of patients with other chronic somatic illnesses (asthma, diabetes). Patients in both samples reported major impact of chemotherapy on global health status, physical functioning, role functioning, emotional functioning, constipation and diarrhea. Differences between Japanese and Dutch patients were limited to social functioning and financial problems. Japanese patients expressed stronger concerns about their illness than Dutch patients. Results of the Japanese and Dutch patients with breast cancer differed from data in patients with asthma on consequences, timeline, concern and emotional response. Results of Japanese patients differed from patients with type 2 diabetes on timeline and concern, whereas Dutch patients differed on timeline and consequences. Japanese and Dutch breast cancer patients have-overall-similar illness perceptions and QOL responses and are aware of the typical characteristics of their disease. The results support the feasibility of cross-cultural psychosocial research in oncology and offer implications for clinical interventions which impact on self-efficacy to empower patients with breast cancer.

Routine monitoring of quality of life for patients with breast cancer: an acceptability and field test.

As part of the development of a quality of life monitor for women with breast cancer, a qualitative acceptability test was conducted among 10 patients, to assess their suggestions for improvement. Next, a field test was conducted among 50 women with breast cancer receiving radiotherapy, chemotherapy, or both treatments to examine the use of the monitor in daily practice and to assess physicians' and patients' experiences with the monitor. Although patients in general held a positive attitude toward the monitor and compliance was high, patients regularly were unsure about how the quality of life information was used by physicians.

Improved guideline compliance after a 3-year audit of multidisciplinary colorectal cancer care in the western part of the Netherlands.

BACKGROUND: From 2006 to 2008, an audit of the multidisciplinary diagnosis and treatment of colorectal cancer patients in the western part of the Netherlands was carried out. We evaluated whether compliance with guidelines had improved. METHODS: All patients with newly diagnosed and surgically treated colon (n = 1,667) and rectal cancer (n = 544) stage I-III were evaluated. Nine quality indicators were derived from the evidence-based guidelines. In order to compare hospital performances, hospital results were adjusted for casemix differences between hospitals. RESULTS: Colon cancer patients showed an increase in the examination of 10 or more lymph nodes (from 53% to 78%, P < 0.0001). For rectal cancer patients there was an increase in preoperative visualisation of the total colon (63-74%, P = 0.02), MRI (73-85%, P = 0.003), radiotherapy (from 82% to 93% for patients <75 years, P = 0.01) and examination of at least 10 lymph nodes (40-55%, P = 0.004). In 2006, standardised hospital performances differed widely for all quality indicators. Two years later, hospital performances for some quality indicators were more similar. CONCLUSIONS: After the feedback of benchmark information, compliance with guidelines for diagnosis and treatment of colorectal cancer patients improved, and differences between individual hospitals decreased. Although secular trends cannot be ruled out, it is highly likely that these results can be attributed to the audit.

Illness perceptions and quality of life in Japanese and Dutch patients with non-small-cell lung cancer.

This study examined quality of life (QOL) and illness perceptions in Dutch and Japanese patients with non-small-cell lung cancer, thereby extending the body of knowledge on cultural differences and psychosocial aspects of this illness. 24 Dutch and 22 Japanese patients with non-small-cell lung cancer filled out questionnaires on three occasions: immediately before chemotherapy, 1 week later, and 8 weeks after the initial chemotherapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assessed QOL, and the Brief Illness Perception Questionnaire (B-IPQ) illness perceptions. Scores on several QOL measures indicated (a) major impact of first chemotherapy sessions, and (b) some tendency to returning to baseline measures at 8 weeks. Differences between Japanese and Dutch samples were found on five EORTC QLQ-C30 dimensions: global health status, emotional functioning, social functioning, constipation, and financial difficulties, with the Dutch patients reporting more favorable scores. Regarding illness perceptions, Japanese patients had higher means on perceived treatment control and personal control, expressing a higher sense of belief in the success of medical treatment than Dutch patients. In both Japanese and Dutch patients, impact of chemotherapy on QOL was evident. Some differences in illness perceptions and QOL between the two samples were observed, with implications for integral medical management. Both samples reported illness perceptions that reflect the major consequences of non-small-cell lung cancer. Incorporating symptom reports, illness perceptions, and QOL into medical management may have positive consequences for patients with non-small-cell lung cancer.

[Antitumour effects of bisphosphonates in breast cancer]. / Antitumoreffect van bisfosfonaten bij mammacarcinoom.

Pre-clinical and clinical studies increasingly suggest that the most potent nitrogen-containing bisphosphonates have antitumour effects. Bisphosphonates inhibit osteoclast-mediated bone resorption, and can thus delay the spread of skeletal metastases. Bisphosphonates might also inhibit tumour growth outside the skeleton by inducing apoptosis and inhibiting proliferation, adhesion, invasion, and angiogenesis of tumour cells. Recent trials suggest a possible synergistic antitumour effect between bisphosphonates and chemotherapy. A mechanism of action for bisphosphonates that could explain their possible antitumour effect and their synergy with chemotherapy is speculative and demands further investigation. The role of bisphosphonates in primary neoadjuvant treatment of breast cancer is promising, but must be further investigated.