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PubMed | Bernhoven Hospital, Elisabeth TweeSteden Hospital, VieCuri Hospital, Elisabeth Tweesteden Hospital and 2 more.
Type: Journal Article | Journal: Acta oncologica (Stockholm, Sweden) | Year: 2016

Although the spectrum of systemic treatment for metastatic colorectal cancer (mCRC) has widened, there is a paucity of evidence for the feasibility and optimal use of these systemic agents in elderly patients. The present study provides real world data on the age-related systemic treatment and survival of CRC patients with non-resectable metachronous metastases.All consecutive patients with non-resectable metastases from primary resected CRC were extracted from the Eindhoven area of the Netherlands Cancer Registry (NCR). Patients receiving palliative systemic therapy were enrolled (n=385). Systemic treatment and survival were analyzed according to age at diagnosis of metastases.Patients aged75 years more often received first-line single-agent chemotherapy than their younger counterparts (63% vs. 32%, p<.0001). First-line single-agent chemotherapy was often prescribed without additional targeted therapy (78%). Advanced age (75 years) was associated with a lower probability of receiving all active cytotoxic agents compared to patients aged <60 years at time of diagnosis of metastases (odds ratio (OR) 0.2, 95% CI 0.10-0.77). In a multivariable Cox regression analysis with adjustment for age and other relevant prognostic factors, the total number of received systemic agents was the only predictor of death (hazard ratio (HR) 0.7, 95% CI 0.61-0.81).The beneficial effect of treatment with all active systemic agents on survival (simultaneously or sequentially prescribed) should be taken into account when considering systemic therapy in patients with mCRC. In light of our results, future studies are warranted to clarify the role of potential targeted therapy in elderly mCRC patients, who are often not candidates for combination chemotherapy and treatment with all active cytotoxic agents.


Saadatmand S.,Erasmus Medical Center | Bretveld R.,Netherlands Comprehensive Cancer Organization | Siesling S.,Netherlands Comprehensive Cancer Organization | Siesling S.,University of Twente | Tilanus-Linthorst M.M.A.,Erasmus Medical Center
BMJ (Online) | Year: 2015

Objectives: To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy. Design: Prospective nationwide population based study. Setting: Nationwide Netherlands Cancer Registry. Participants: Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173 797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80 228) and 2006-12 (n=93 569). Main outcomemeasures: Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately. Results: Compared with 1999-2005, patients from 2006-12 had smaller (≤T1 65% (n=60 570) v 60% (n=48 031); P<0.001), more often lymph node negative (N0 68% (n=63 544) v 65% (n=52 238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56 402) v 53% (n=42 185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0:1.25, 1.17 to 1.32). Conclusions: Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vital. © BMJ Publishing Group Ltd 2015.


Bokhorst L.P.,Erasmus Medical Center | Kranse R.,Netherlands Comprehensive Cancer Organization | Venderbos L.D.F.,Erasmus Medical Center | Salman J.W.,Erasmus Medical Center | And 4 more authors.
European Urology | Year: 2015

Screening for prostate cancer (PCa) results in a favorable stage shift. However, even if screening did not result in a clinically apparent lower stage or grade, it might still lead to less disease recurrence after treatment with curative intent (radical prostatectomy [RP] and radiation therapy [RT]) because the tumor had less time to develop outside the prostate. The outcome after treatment could also differ because of variations in treatment quality (eg, radiation dosage/adjuvant hormonal therapy). To test these hypotheses, we compared differences in the treatment quality of the screening and control arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam and disease-free survival (DFS) after curative treatment in PCa patients with similar stage and grade. A total of 2595 men were initially treated with RP or RT. In the control arm, RT was more often combined with hormonal therapy; treatment dosage was often ≥69 Gy. This most likely resulted from changes over time in treatment that coincided with the later detection in the control arm. DFS was higher in the screening arm in all risk groups. After correction for lead time, these differences were minimal, however. We concluded that treatment quality differed between the screening and control arms of the ERSPC Rotterdam. RT quality was especially superior in the control arm with higher dosages and more often RT in combination with hormonal therapy. Despite these differences favoring the control arm, DFS differences were minimal. Patient summary We looked at differences in prostate cancer (PCa) treatment and outcome after PCa treatment in men diagnosed after screening and men diagnosed after normal clinical practice. Treatment differed with superior treatment given to men diagnosed in normal clinical practice. We propose a likely explanation for this apparently counterintuitive finding (progressive insight combined with, on average, a later detection of tumors in unscreened men). Although unscreened men received better treatment, this advantage seemed to be outweighed by the advantage associated with the earlier detection, on average, of the tumor in screened men. Trial registration ISRCTN49127736 © 2014 European Association of Urology.


Wink K.C.J.,Maastricht University | Belderbos J.S.A.,Netherlands Cancer Institute | Dieleman E.M.T.,Amsterdam Medical Center | Rossi M.,Netherlands Cancer Institute | And 7 more authors.
Radiotherapy and Oncology | Year: 2016

Background and purpose The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. Material and methods A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS). Results No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p = 0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p = 0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p = 0.02 and 0.03). Conclusions Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial. © 2015 Elsevier Ireland Ltd. All rights reserved.


Vos E.L.,Netherlands Cancer Institute | Voogd A.C.,Netherlands Comprehensive Cancer Organization | Voogd A.C.,Maastricht University | Verhoef C.,Netherlands Cancer Institute | And 4 more authors.
British Journal of Surgery | Year: 2015

Background: Although evidence for the benefits of preoperative MRI in breast cancer is lacking, use of MRI is increasing and characterized by large interhospital variation. The aim of the study was to evaluate MRI use and surgical outcomes retrospectively. Methods: Women with invasive breast cancer (pT1–3) or ductal carcinoma in situ (DCIS), diagnosed in 2011–2013, were selected from the Netherlands Cancer Registry and subdivided into the following groups: invasive cancer, high-grade DCIS, non-palpable cancer, age 40 years or less, and invasive lobular cancer. Associations between preoperative MRI use and initial mastectomy, resection margin after breast-conserving surgery (BCS), re-excision after BCS, and final mastectomy were analysed. Results: In total, 5514 women were included in the study; 1637 (34·1 per cent) of 4801 women with invasive cancer and 150 (21·0 per cent) of 713 with DCIS had preoperative MRI. Positive resection margins were found in 18·1 per cent women who had MRI and in 15·1 per cent of those who did not (adjusted odds ratio (OR) 1·20, 95 per cent c.i. 1·00 to 1·45), with no differences in subgroups. Re-excision rates were 9·8 per cent in the MRI group and 7·2 per cent in the no-MRI group (adjusted OR 1·33, 1·04 to 1·70), with no differences in subgroups. In the MRI group, 38·8 per cent of patients ultimately underwent mastectomy, compared with 24·2 per cent in the no-MRI group (adjusted OR 2·13, 1·87 to 2·41). This difference was not found for patients aged 40 years or less, or for those diagnosed with lobular cancer. Conclusion: No subgroup was identified in which preoperative MRI influenced the risk of margin involvement or re-excision rate after BCS. MRI was significantly associated with more extensive surgery, except in patients aged 40 years or less and those with invasive lobular cancer. These results suggest that use of preoperative MRI should be more targeted, and that general, widespread use be discouraged. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd


PubMed | Wageningen University, VU University Amsterdam, University of Tilburg, Netherlands Comprehensive Cancer Organization and Maastricht University
Type: Journal Article | Journal: The oncologist | Year: 2016

The population of colorectal cancer (CRC) survivors is growing and many survivors experience deteriorated health-related quality of life (HRQoL) in both early and late post-treatment phases. Identification of CRC survivors at risk for HRQoL deterioration can be improved by using prediction models. However, such models are currently not available for oncology practice. As a starting point for developing prediction models of HRQoL for CRC survivors, a comprehensive overview of potential candidate HRQoL predictors is necessary. Therefore, a systematic literature review was conducted to identify candidate predictors of HRQoL of CRC survivors. Original research articles on associations of biopsychosocial factors with HRQoL of CRC survivors were searched in PubMed, Embase, and Google Scholar. Two independent reviewers assessed eligibility and selected articles for inclusion (N = 53). Strength of evidence for candidate HRQoL predictors was graded according to predefined methodological criteria. The World Health Organizations International Classification of Functioning, Disability and Health (ICF) was used to develop a biopsychosocial framework in which identified candidate HRQoL predictors were mapped across the main domains of the ICF: health condition, body structures and functions, activities, participation, and personal and environmental factors. The developed biopsychosocial ICF framework serves as a basis for selecting candidate HRQoL predictors, thereby providing conceptual guidance for developing comprehensive, evidence-based prediction models of HRQoL for CRC survivors. Such models are useful in clinical oncology practice to aid in identifying individual CRC survivors at risk for HRQoL deterioration and could also provide potential targets for a biopsychosocial intervention aimed at safeguarding the HRQoL of at-risk individuals.More and more people now survive a diagnosis of colorectal cancer. The quality of life of these cancer survivors is threatened by health problems persisting for years after diagnosis and treatment. Early identification of survivors at risk of experiencing low quality of life in the future is thus important for taking preventive measures. Clinical prediction models are tools that can help oncologists identify at-risk individuals. However, such models are currently not available for clinical oncology practice. This systematic review outlines candidate predictors of low quality of life of colorectal cancer survivors, providing a firm conceptual basis for developing prediction models.


PubMed | University Utrecht, Netherlands Comprehensive Cancer Organization, Netherlands Cancer Institute and Diakonessenhuis Utrecht
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2016

Over recent years, adjuvant systemic treatment guidelines (AST) for early-stage breast cancer have changed considerably. We aimed to assess the impact of these guideline changes on the administration of AST in early-stage breast cancer patients and to what extent these guidelines are adhered to at a nation-wide level. We used Netherlands Cancer Registry data to describe trends in AST prescription, adherence to AST guidelines, and to identify clinicopathological determinants of nonadherence. Between 1990 and 2012, 231,648 Dutch patients were diagnosed with early breast cancer, of whom 124,472 received AST. Adjuvant endocrine treatment (ET) use increased from 23% of patients (1990) to 56% (2012), and chemotherapy from 11 to 44%. In 2009-2012, 8% of patients received ET and 3% received chemotherapy without guideline indication. Conversely, 10-29% of patients did not receive ET and chemotherapy, respectively, despite a guideline indication. Unfavorable clinicopathological characteristics generally decreased the chance of undertreatment and increased the chance for overtreatment. Remarkable was the increased chance of ET undertreatment in younger women (RR<35 vs 60-69years 1.79; 95% CI 1.30-2.47) and in women with HER2+ disease (RR 1.64; 95% CI 1.46-1.85). Over the years, AST guidelines expanded resulting in much more Dutch early breast cancer patients receiving AST. In the majority of cases, AST administration was guideline concordant, but the high frequency of chemotherapy undertreatment in some subgroups suggests limited AST guideline support in these patients.


PubMed | Netherlands Comprehensive Cancer Organization, Netherlands Cancer Institute and Maxima Medical Center
Type: Journal Article | Journal: Urologic oncology | Year: 2016

To assess temporal trends in radical cystectomy (RC) and pelvic lymph node dissection (PLND) and the effect of centralization of care in the Netherlands between 2006 and 2012.This nationwide population-based study included 3524 patients from the Netherlands Cancer Registry who underwent RC as the primary treatment for cT1-4a, N0 or Nx, M0 urothelial carcinoma. Annual application rates of PLND, median LNC, and rates of node-positive disease (pN+) were compared by linear-by-linear association. Multivariable logistic regression was performed to identify patients and hospital characteristics associated with PLND and LNC10, and to study associations between LNC and pN+disease.In total, 3,191 (91%) patients had PLND during RC and the use increased from 84% in 2006 to 96% in 2012 (P<0.001). Owing to centralization of care in 2010 (at least 10RCs/y/hospital), significantly more patients were treated in high-volume hospitals (20RC per year) in 2011 and 2012. PLND use was highest in males, younger patients and in academic, teaching, and high-volume hospitals (20RC per year). In 2012, PLND application rates were comparable for academic, teaching, and nonteaching hospitals (P = 0.344). Median LNC increased from 7 in 2006 to 13 in 2012 (P<0.001), 55% had an LNC10 (63% in 2012). Furthermore, lymph node count (LNC)10 was associated with cT3-4a and, pN+disease, R0 and treatment in academic, teaching, or high-volume hospitals (20RC per year). Rate of pN+disease increased from 18% to 24% between 2006 and 2012 (P = 0.014). This trend was significantly associated with increased LNC on a continuous scale (odds ratio = 1.03).After centralization of care, PLND during RC for cT1-4a, N0 or Nx, M0 urothelial carcinoma has become standard in all types of Dutch hospitals. The increase in LNC between 2006 and 2012 was associated with a higher incidence of pN+disease and suggests more adequate template extension and adherence to contemporary guidelines in recent years.


PubMed | TU Dresden, Netherlands Comprehensive Cancer Organization, Amsterdam Medical Center, Maastricht University and Netherlands Cancer Institute
Type: Journal Article | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2016

The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome.A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS).No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p=0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p=0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p=0.02 and 0.03).Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial.


PubMed | Amsterdam Rehabilitation Research Center Reade, University of Tilburg and Netherlands Comprehensive Cancer Organization
Type: Journal Article | Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer | Year: 2016

In an equitable healthcare system, healthcare utilization should be predominantly explained by patient-perceived need and clinical need factors. This study aims to analyze whether predisposing, enabling, and need factors are associated with the utilization of supportive care (i.e., dietary care, oncological nursing care, physical therapy, psychological care, or participation in a rehabilitation program consisting of an exercise component and a psycho-educational component) among survivors of colorectal cancer in the Netherlands.Cross-sectional data of 3957 survivors of colorectal cancer (1-11years after diagnosis) were used. Clinical data from the Eindhoven Cancer Registry were linked to questionnaire data from the PROFILES registry. Regression analyses were used to examine which predisposing, enabling, and need factors were associated with self-reported utilization of supportive care.Utilization of supportive care was primarily associated with younger age, patient-perceived need (i.e., lower physical health, anxious mood, depressive mood, and fatigue), and clinical need (i.e., tumor stage, radiotherapy, chemotherapy, comorbidity, having a stoma and lower BMI) factors.In the Netherlands, utilization of supportive care by survivors of colorectal cancer is primarily associated with younger age, patient-perceived need, and clinical need factors. Apart from the association with younger age, the utilization of supportive care services seems to be quite equitable. Further research is needed to determine whether there is indeed inequity in the provision of supportive care to older survivors, or whether older survivors are less in need of supportive care.

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