Pauline A. J. Vissers

Socio-economic implications of cancer survivorship: results from the PROFILES registry.

INTRODUCTION The goal of this large population-based study was to examine the socio-economic implications of cancer survivorship. METHODS Individuals alive and diagnosed with colorectal cancer and melanoma between 1998 and 2007 or Hodgkin lymphoma, non-Hodgkin lymphoma or multiple myeloma between 1999 and 2008 as registered in the Eindhoven Cancer Registry received a questionnaire on work changes and problems with obtaining a new (or extended) health care insurance, life insurance or a home loan; 70% (n = 2892) responded. RESULTS Results showed that 28% of all cancer patients experienced changes in their work situation after cancer. Most of them switched to part-time work or stopped working entirely. Patients (3.4%) who tried to obtain a different or upgrade their health care insurance experienced problems and in most cases, these were eventually resolved. Problems with life insurance were somewhat more common with 18% of those who tried to obtain a life insurance experiencing problems. The majority of these patients was rejected by the insurance company (61%) or was accepted at a higher premium (22%). Of the 21% who tried to obtain a home loan, 9% experienced problems. However, 22.2% got accepted eventually, 27.8% got accepted but at a higher mortgage payment and 22.2% got rejected but were eventually accepted by another bank. CONCLUSIONS Almost a third of cancer survivors experienced changes in their work situation after cancer. Problems with obtaining health insurance, life insurance and home loans were also common.

Response rates for patient-reported outcomes using web-based versus paper questionnaires: comparison of two invitational methods in older colorectal cancer patients.

Background Improving questionnaire response rates is an everlasting issue for research. Today, the Internet can easily be used to collect data quickly. However, collecting data on the Internet can lead to biased samples because not everyone is able to access or use the Internet. The older population, for example, is much less likely to use the Internet. The Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) registry offers a platform to collect Web-based and paper questionnaires and to try different measures to improve response rates. Objective In this study, our aim was to study the influence of two methods of invitation on the response rate. Our second aim was to examine the preference of questionnaire mode of administration (paper or Web-based) for the older patient in particular. Methods To test these two invitational methods, 3406 colorectal cancer patients between ages 18 and 85 years received an invitation containing an access code for the Web-based questionnaire. They could also request a paper questionnaire with an included reply card (paper-optional group). In contrast, 179 randomly selected colorectal cancer patients received a paper questionnaire with the invitation (paper-included group). They could also choose to fill out the Web-based questionnaire with the included access code. Results Response rates did not differ between the paper-optional and the paper-included groups (73.14%, 2491/3406 and 74.9%, 134/179, P=.57). In the paper-optional group, online response was significantly higher when compared to the paper-included group (41.23%, 1027/2491 vs 12.7%, 17/134, P<.001). The majority of online respondents responded after the first invitation (95.33%, 979/1027), which was significantly higher than the paper respondents (52.19%, 764/1464, P<.001). Respondents aged 70 years and older chose to fill out a paper questionnaire more often (71.0%, 677/954). In the oldest age group (≥80 years), 18.2% (61/336) of the respondents filled out a Web-based questionnaire. Conclusions The lack of difference in response rates between invitation modes implies that researchers can leave out a paper questionnaire at invitation without lowering response rates. It may be preferable not to include a paper questionnaire because more respondents then will fill out a Web-based questionnaire, which will lead to faster available data. However, due to respondent preference, it is not likely that paper questionnaires can be left out completely in the near future.

Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another?

Background:Metformin, statin and aspirin use seem associated with decreased mortality in cancer patients, though, without adjusting for one another. Independent associations of these drugs with overall mortality after colorectal cancer (CRC) diagnosis within glucose-lowering drugs (GLDs) users were assessed.Methods:Patients starting GLDs before CRC diagnosis (1998–2011) were selected from the Eindhoven Cancer Registry linked with the PHARMO Database Network. The Cox regression model, with time since CRC diagnosis, included time-dependent variables of cumulative exposure to metformin, statins and aspirin after cancer diagnosis and time-dependent ever-never terms for drug exposure.Results:A total of 1043 patients used GLDs before CRC diagnosis; 666 (64%) used metformin, 639 (61%) used statins and 490 (47%) used aspirin after CRC diagnosis. Multivariable analyses revealed that longer cumulative exposure to metformin was not associated with overall mortality (HRCumulative exposure/6 months 1.02; 95% CI 0.97–1.07), whereas the favourable effect of statins increased with cumulative exposure (HRCumulative exposure/6 months 0.93; 95% CI 0.89–0.98). No association between aspirin use and overall mortality was seen (HRCumulative exposure/6 months 0.98; 95% CI 0.93–1.03).Conclusions:No independent association between cumulative exposure to metformin, aspirin and overall mortality was found. Cumulative exposure to statins after CRC diagnosis was associated with lower overall mortality, supporting a drug effect of statins among GLDs users.

Colorectal cancer, diabetes and survival: Epidemiological insights

Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes and cancer. One of the key issues identified for further investigation was the need for a better understanding of whether diabetes influences cancer prognosis above and beyond the prognosis conferred by each disease state independently. Whether the worsened survival of CRC patients with diabetes could be explained by less favourable patient-, tumour- and treatment-related characteristics has also been evaluated in numerous recent studies. However, as most studies did not account for all the various potential confounders, such as cancer stage, comorbidities and body mass index (BMI) in their analyses, the current evidence for the association between diabetes and survival in CRC patients remains inconclusive. Nevertheless, based on multiple examples in the literature, the present review demonstrates that diabetes affects the presentation of CRC as well as its treatment and outcome, which may then result in lower overall rates of survival in patients with, compared to those without, diabetes.

Treatment-related differences in health related quality of life and disease specific symptoms among colon cancer survivors: Results from the population-based PROFILES registry

BACKGROUND The goal of this study was to compare health related quality of life (HRQoL) and disease-specific symptoms between colon cancer patients treated with surgery only (SU) and surgery and adjuvant chemotherapy (SU+adjCT). Results were stratified for those aged <70 and ⩾70years. HRQoL of patients was also compared with an age- and sex-matched normative population. METHODS Patients diagnosed with colon cancer between January 2000 and June 2009, as registered within the population-based Eindhoven Cancer Registry, received a questionnaire on HRQoL (European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire version 3.0 (QLQ-C30)) and disease-specific symptoms (EORTC QLQ-Colorectal 38 (EORTC QLQ-CR38)) in 2010. The first was also completed by the normative population (n=685). RESULTS 1606 (72%) colon cancer survivors responded to our questionnaire. 1542 colon cancer patients treated with SU (n=1031) or SU+adjCT (n=493) were included in this study. In colon cancer patients aged <70years and aged ⩾70 no statistical significant differences on the subscales of the EORTC QLQ-C30 or the EORTC QLQ-CR38 were observed between patients treated with SU and SU+adjCT. Colon cancer patients aged <70years either treated with SU or SU+adjCT reported significantly more insomnia, diarrhoea and financial problems compared with the normative population. No differences in HRQoL were found between colon cancer patients aged ⩾70years either treated with SU or SU+adjCT and the normative population. CONCLUSION No differences in HRQoL and disease-specific symptoms were found between patients treated with SU versus SU+adjCT in both younger and elderly colon cancer patients. Withholding patients adjCT, based on concerns for long-term HRQoL or disease-specific symptoms does therefore not seem plausible.

Association Between Metformin Use and Mortality in Patients With Prostate Cancer: Explained by Confounding by Indication?

TO THE EDITOR: Margel et al 1 recently reported on a populationbased retrospective cohort study that used a unique large database to investigate patients with prostate cancer diagnosed with incident diabetes. Increased cumulative duration of metformin exposure after prostate cancer diagnosis was associated with decreases in both all-cause and prostate cancer–specific mortality among men with diabetes. The study showed that prostate cancer–specific mortality even decreased by 24% for each additional 6 months of metformin use after the diagnosis of prostate cancer. Although the approach used in this study did circumvent numerous potential limitations and biases, 2 on the basis of the authors’ conclusions and study design, we have a few comments and requests for clarification. With regard to their statistical analyses, the effects of cumulative duration of exposure to metformin on mortality were assessed by using a Cox proportional hazards model in which drug exposures after prostate cancer diagnosis were modeled as time-dependent covariates. The comparison was not exclusively between users who had different durations of exposure, but also between users and nonusers of the drug. This means that in the time-dependent model, patients not using metformin were included in the analysis as 0 for cumulative use of metformin. Modeling the line for this specific hazard ratio (HR) of cumulative metformin use could be expected to be greatly influenced by events in the nonusers, given that patients using and not using metformin might differ in their previous susceptibility to dying as a result of cancer. As a consequence, these results might be affected by confounding by indication, which could not be avoided by the inclusion of cumulative drug exposure exclusively, as supposed in this analysis. It can be shown algebraically that with the inclusion of an ever-never termformetforminuseinthemodel,theHRofthecumulativeeffectterm

The role of personality in the course of health-related quality of life and disease-specific health status among colorectal cancer survivors: A prospective population-based study from the PROFILES registry

Abstract Background. Prospective studies in various cardiovascular populations show that Type D personality predicted impaired health-related quality of life (HRQoL) and disease-specific health status. We examined the effect of negative affectivity (NA), social inhibition (SI) and their combined effect (Type D personality) on HRQoL and disease-specific health status among colorectal cancer (CRC) patients. Methods. CRC patients diagnosed between 2000 and 2009, as registered in the Dutch population-based Eindhoven Cancer Registry, received questionnaires on Type D personality (DS14), HRQoL (EORTC QLQ-C30) and disease-specific health status (EORTC QLQ-CR38) in 2010, 2011 and 2012. Results. Response rates were 73% (n = 2625), 83% (n = 1643) and 82% (n = 1458), respectively. Analyses were done on those completing at least two questionnaires (n = 1735). Individuals with Type D (NA+/SI+; 19%) and high NA (NA+/SI-; 11%) reported a significantly worse HRQoL and disease-specific health status compared to NA-/SI+ and NA-/SI-. Differences were stable over time. Linear mixed effects models showed that Type Ds had a lower quality of life, cognitive and emotional functioning, more insomnia, diarrhea, gastrointestinal, defecation and stoma-related problems and poor body image and future perspective compared to the reference group (NA-/SI-), even after controlling for sociodemographic and clinical variables. High NA individuals (NA+/SI-) reported similar poor health outcomes as Type Ds. However, they also reported lower social functioning and more fatigue, pain, micturition- and financial problems, while Type Ds reported more constipation, sexual problems and less sexual enjoyment. Conclusions. Type D personality and high NA both have a significant negative stable impact on HRQoL and disease-specific health status among CRC patients.

Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis

Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel–Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07–0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel–Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84–1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel–Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer.

The Impact of Body Mass Index and Waist Circumference on Health-related Quality of Life Among Colorectal Cancer Survivors: Results from the PROFILES Registry

ABSTRACT Background: We aimed to assess the association of waist circumference (WC) and body mass index (BMI) with health-related quality of life (HRQL) among colorectal cancer (CRC) survivors. Methods: CRC survivors diagnosed between 2000 and 2009 completed questionnaires in August 2013 (with self-reported weight, height, and self-assessed WC) and January 2014 (with HRQL using the EORTC-QLQ-C30). Clinical characteristics were retrieved from the Netherlands Cancer Registry. In multivariable linear regression analyses associations of BMI only, WC only and both BMI and WC with HRQL outcomes were assessed. Results: 1,111 CRC survivors were included of whom 34% had a normal weight (18.5 ≤ BMI < 25 kg/m2), 49% had overweight (25 ≤ BMI < 30 kg/m2), 17% had obesity (BMI ≥ 30 kg/m2), and 44% had an increased WC (i.e., >102 and >88 cm for men and women, respectively). Both BMI and WC were separately associated with worse global health status, functioning, and more symptoms of fatigue. Increased WC was associated with lower physical, role and emotional functioning, regardless of BMI, with average differences ranging between 3 and 5 points. Conclusion: Future research on HRQL among CRC survivors should consider both BMI and WC. Furthermore, weight reduction trials should not only focus on general weight loss but also on the loss of abdominal fat.

Propranolol and survival from breast cancer: a pooled analysis of European breast cancer cohorts

BackgroundPreclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all-cause mortality in eight European cohorts.MethodsIncident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all-cause mortality were available for five and eight cohorts, respectively. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality by propranolol and non-selective beta-blocker use. HRs were pooled across cohorts using meta-analysis techniques. Dose–response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis.ResultsThe combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all-cause mortality respectively. Overall, there was no association between propranolol use after diagnosis of breast cancer and breast cancer-specific or all-cause mortality (fully adjusted HR = 0.94, 95% CI, 0.77, 1.16 and HR = 1.09, 95% CI, 0.93, 1.28, respectively). There was little evidence of a dose–response relationship. There was also no association between propranolol use before breast cancer diagnosis and breast cancer-specific or all-cause mortality (fully adjusted HR = 1.03, 95% CI, 0.86, 1.22 and HR = 1.02, 95% CI, 0.94, 1.10, respectively). Similar null associations were observed for non-selective beta-blockers.ConclusionsIn this large pooled analysis of breast cancer patients, use of propranolol or non-selective beta-blockers was not associated with improved survival.