Comprehensive Cancer Center the Netherlands

Utrecht, Netherlands

Comprehensive Cancer Center the Netherlands

Utrecht, Netherlands
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Sant M.,Instituto Nazionale dei Tumori | Minicozzi P.,Instituto Nazionale dei Tumori | Mounier M.,University of Burgundy | Anderson L.A.,Queen's University of Belfast | And 9 more authors.
The Lancet Oncology | Year: 2014

Background: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997-99, 2000-02, 2003-05, 2006-08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings: We analysed 560 444 cases. From 1997-99 to 2006-08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7-43·4] to 55·4% [54·6-56·2], p<0·0001), follicular lymphoma (58·9% [57·3-60·6] to 74·3% [72·9-75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6-33·9] to 54·4% [52·5-56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7-56·2] to 61·9% [57·0-66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1-76·0] to 79·3% [78·4-80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1-67·1] to 69·0% [68·1-69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0-30·6] to 39·6% [38·8-40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7-32·0] to 41·1% [39·0-43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9-13·3] to 14·8% [14·2-15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7-71·8] to 74·9% [73·8-75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. © 2014 Elsevier Ltd.


De Angelis R.,Instituto Superiore Of Sanita | Sant M.,Fondazione IRCSS Instituto Nazionale dei Tumori | Coleman M.P.,London School of Hygiene and Tropical Medicine | Francisci S.,Instituto Superiore Of Sanita | And 12 more authors.
The Lancet Oncology | Year: 2014

Background: Cancer survival is a key measure of the effectiveness of health-care systems. EUROCARE-the largest cooperative study of population-based cancer survival in Europe-has shown persistent differences between countries for cancer survival, although in general, cancer survival is improving. Major changes in cancer diagnosis, treatment, and rehabilitation occurred in the early 2000s. EUROCARE-5 assesses their effect on cancer survival in 29 European countries. Methods: In this retrospective observational study, we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008. Uniform quality control procedures were applied to all datasets. For patients diagnosed 2000-07, we calculated 5-year relative survival for 46 cancers weighted by age and country. We also calculated country-specific and age-specific survival for ten common cancers, together with survival differences between time periods (for 1999-2001, 2002-04, and 2005-07). Findings: 5-year relative survival generally increased steadily over time for all European regions. The largest increases from 1999-2001 to 2005-07 were for prostate cancer (73·4% [95% CI 72·9-73·9] vs 81·7% [81·3-82·1]), non-Hodgkin lymphoma (53·8% [53·3-54·4] vs 60·4% [60·0-60·9]), and rectal cancer (52·1% [51·6-52·6] vs 57·6% [57·1-58·1]). Survival in eastern Europe was generally low and below the European mean, particularly for cancers with good or intermediate prognosis. Survival was highest for northern, central, and southern Europe. Survival in the UK and Ireland was intermediate for rectal cancer, breast cancer, prostate cancer, skin melanoma, and non-Hodgkin lymphoma, but low for kidney, stomach, ovarian, colon, and lung cancers. Survival for lung cancer in the UK and Ireland was much lower than for other regions for all periods, although results for lung cancer in some regions (central and eastern Europe) might be affected by overestimation. Survival usually decreased with age, although to different degrees depending on region and cancer type. Interpretation: The major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in Europe. Likely explanations of differences in survival between countries include: differences in stage at diagnosis and accessibility to good care, different diagnostic intensity and screening approaches, and differences in cancer biology. Variations in socioeconomic, lifestyle, and general health between populations might also have a role. Further studies are needed to fully interpret these findings and how to remedy disparities. Funding: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation, Cariplo Foundation. © 2014 Elsevier Ltd.


Peters T.T.A.,University of Groningen | Van Dijk B.A.C.,Comprehensive Cancer Center the Netherlands | Van Dijk B.A.C.,University of Groningen | Roodenburg J.L.N.,University of Groningen | And 2 more authors.
Annals of Surgical Oncology | Year: 2014

Background: Multiple factors have been identified as predictors of complication after head and neck surgery. However, little is known about the exact role of different comorbid conditions in the development of postoperative complications. This question is especially interesting in the elderly population. The aim of this study was to investigate the association between comorbidity and types of postoperative complications with special attention to age differences. Methods: A retrospective analysis was performed of 1,201 major surgical interventions for head and neck malignancies in a tertiary referral center between 1995 and 2010. The Adult Comorbidity Evaluation 27 (ACE-27) index was used to analyze severity (mild, moderate, and severe comorbidity) and type (12 different organ systems) of comorbidity. The Clavien-Dindo index was used to evaluate grade and type of complications after treatment. Results: In univariate analysis gender, comorbidity, stage, mandibulectomy, total laryngectomy, neck dissection, and length of surgery significantly predicted grade of complication. In a multivariate analysis, complication was predicted by age, stage, length of surgery, and various comorbidities. After specification of the complications, age was only a predictor of medical complications; tumor stage was a significant factor in surgical complications. Length of surgery was the only significant variable in all types of complications. Conclusions: Specific comorbidities are associated with specific complications; however, age itself seems not to be a contraindication for major head and neck surgery. With careful preoperative assessment and risk analysis, physicians can better individualize treatment recommendations. © 2013 Society of Surgical Oncology.


Haasbeek C.J.A.,VU University Amsterdam | Palma D.,VU University Amsterdam | Visser O.,Comprehensive Cancer Center The Netherlands | Lagerwaard F.J.,VU University Amsterdam | And 2 more authors.
Annals of Oncology | Year: 2012

Background: Elderly patients with stage I non-small-cell lung cancer are less likely to undergo curative treatment. However, the introduction of new treatment options such as stereotactic ablative radiotherapy (SABR) may improve treatment rates. We evaluated time trends in treatment patterns and survival in the entire Netherlands population for patients diagnosed between 2001 and 2009. Patients and methods: Details of 4605 elderly Dutch patients were obtained from the Netherlands Cancer Registry, containing data on all cancer patients in a population of 16 million. Three consecutive time periods were studied: 2001-2003 (A, before SABR became available), 2004-2006 (B, increasing availability), and 2007-2009 (C, full availability). Results: Between period A and C, there was a 7% absolute reduction in patients going untreated, corresponding to an 8-month improvement in median survival (P < 0.001). Radiotherapy utilization increased from 31% to 38%, whereas surgical utilization remained constant (37%). Significant improvements in survival were observed in the radiotherapy subgroup (P < 0.001) and surgery subgroup (P < 0.001), not in patients going untreated. There was no evidence of stage migration. Conclusions: Population-based increases in survival of elderly stage I lung cancer patients were seen between 2001 and 2009. The introduction of SABR correlated with a decline in the number of untreated patients. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Dings P.J.M.,Radboud University Nijmegen | Elferink M.A.G.,Comprehensive Cancer Center the Netherlands | Strobbe L.J.A.,Canisius Wilhelmina Hospital | De Wilt J.H.W.,Radboud University Nijmegen
Annals of Surgical Oncology | Year: 2013

Background: The absolute number of involved axillary lymph nodes (LNs) is considered the most important prognostic factor in breast cancer. Over the last decade, several studies indicated that the lymph node ratio (LNR) might predict outcome better than the number of positive LNs. In this study we test the applicability of earlier published LNR cutoff values and study the prognostic value of the LNR on a nationwide level. Methods: A nationwide population-based study was performed, using data from the Netherlands Cancer Registry, including all women diagnosed with node-positive breast cancer between 1999 and 2005 (N = 25,315). Patients were divided into 3 LNR risk groups (low, ≤0.20; intermediate, 0.21-0.65; and high, >0.65). Kaplan-Meier survival analysis was performed. In order to evaluate whether LNR was associated with overall survival (OS), Cox proportional hazards modeling was used. Results: For the entire cohort, 5- and 10-year OS rates were 78 % and 62 %, respectively. The number of positive LNs correlated with OS (5-year OS 84 %, 72 %, and 55 % for patients with 1-3, 4-9, and 10 or more positive LNs, respectively, P <.001). LNR also correlated with OS (5-year OS 86 %, 75 %, and 54 % for low-, intermediate-, and high-risk groups, respectively, P <.001). In the multivariable analysis, the risk of death increased with increasing LNR (P <.001). Conclusions: The LNR has an important prognostic value in node-positive patients, independent of traditional clinicopathological factors. LNR should be added as an independent prognostic variable to the current staging system. © 2013 Society of Surgical Oncology.


Coumans F.A.W.,University of Twente | Siesling S.,Comprehensive Cancer Center the Netherlands | Siesling S.,University of Twente | Terstappen L.W.M.M.,University of Twente
BMC Cancer | Year: 2013

Background: To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the first metastasis has formed from a primary breast cancer tumor.Methods: The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed TXNXM0 primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T1BNXM0 (25% of total patients with T1BNXM0). Validation of the model was done with data for all patients.Results: From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T1B patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for TXNXM0 from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood.Conclusions: To reduce the rate of distant metastasis in surgically treated TXNXM0 breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be improved by at least 15-fold and combined with technology that minimizes false positives. © 2013 Coumans et al.; licensee BioMed Central Ltd.


Damhuis R.A.M.,Comprehensive Cancer Center the Netherlands | Wijnhoven B.P.L.,Erasmus Medical Center | Plaisier P.W.,Albert Schweitzer Hospital | Kirkels W.J.,Erasmus Medical Center | And 2 more authors.
British Journal of Surgery | Year: 2012

Background: Various definitions are used to calculate postoperative mortality. As variation hampers comparability between reports, a study was performed to evaluate the impact of using different definitions for several types of cancer surgery. Methods: Population-based data for the period 1997-2008 were retrieved from the Rotterdam Cancer Registry for resectional surgery of oesophageal, gastric, colonic, rectal, breast, lung, renal and bladder cancer. Postoperative deaths were tabulated as 30-day, in-hospital or 90-day mortality. Postdischarge deaths were defined as those occurring after discharge from hospital but within 30 days. Results: This study included 40 474 patients. Thirty-day mortality rates were highest after gastric (8·8 per cent) and colonic (6·0 per cent) surgery, and lowest after breast (0·2 per cent) and renal (2·0 per cent) procedures. For most tumour types, the difference between 30-day and in-hospital rates was less than 1 per cent. For bladder and oesophageal cancer, however, the in-hospital mortality rate was considerably higher at 5·1 per cent (+1·3 per cent) and 7·3 per cent (+2·8 per cent) respectively. For gastric, colonic and lung cancer, 1·0 per cent of patients died after discharge. For gastric, lung and bladder cancer, more than 3 per cent of patients died between discharge and 90 days. Conclusion: The 30-day definition is recommended as an international standard because it includes the great majority of surgery-related deaths and is not subject to discharge procedures. The 90-day definition, however, captures mortality from multiple causes; although this may be of less interest to surgeons, the data may be valuable when providing information to patients before surgery. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.


Braakhuis B.J.M.,VU University Amsterdam | Leemans C.R.,VU University Amsterdam | Visser O.,Comprehensive Cancer Center the Netherlands
Oral Oncology | Year: 2014

Background Incidence and survival trends of head and neck squamous cell carcinoma (HNSCC) are essential knowledge for guiding policy making and research. Methods The total population of the Netherlands was studied covering 1989-2011. Two-and five-year survival and age-standardized incidence rates of HNSCC were assessed in relation to site, gender and age (15 years-of-age categories). Results We recorded a statistically significant increase of oral, oropharyngeal and hypopharyngeal carcinoma for males and females of all ages, varying from 0.6% (hypopharynx in males) to 2.7% (oropharynx in females) per year. The incidence of laryngeal carcinoma significantly decreased for males with 2.3% per year; for females the situation was stable. In young adults (below 45 years of age) the incidence figures were different: significant decreasing incidence trends were seen for both genders for carcinomas of the oropharynx, hypopharynx and larynx. Regarding oral carcinoma, no change was observed for the young patient group, but for subsites trends were divergent. Carcinoma of the floor or mouth decreased for both genders, but carcinoma of the tongue rose by a significant 2.8% per year for young males. Five-year survival trends for all ages showed no change for laryngeal carcinoma, a small improvement for oral and hypopharyngeal carcinoma, and a substantial and significant improvement of survival from 36% to 47% survival over the total period for oropharyngeal carcinoma. Conclusion In the Netherlands for the last two decades, the incidence of oral, oropharyngeal and hypopharyngeal squamous cell carcinoma has increased and survival has improved. The incidence of laryngeal carcinoma has decreased in males, and remained unchanged in females; survival from laryngeal carcinoma has not changed. © 2014 Elsevier Ltd. All rights reserved.


Van De Water W.,Leiden University | Kiderlen M.,Leiden University | Bastiaannet E.,Leiden University | Siesling S.,Comprehensive Cancer Center the Netherlands | And 7 more authors.
Journal of the National Cancer Institute | Year: 2014

Background Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients. Methods We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor-positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65-74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided. Results Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P <. 001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P =. 02) than patients in the general population. Conclusions Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial. © The Author 2014. Published by Oxford University Press. All rights reserved.


Gatta G.,Fondazione IRCCS Instituto Nazionale dei Tumori | Mallone S.,Italian National Institute of Health | van der Zwan J.M.,Comprehensive Cancer Center the Netherlands | Trama A.,Fondazione IRCCS Instituto Nazionale dei Tumori | And 3 more authors.
Annals of Oncology | Year: 2013

Background: Complete cancer prevalence data in Europe have never been updated after the first estimates provided by the EUROPREVAL project and referred to the year 1993. This paper provides prevalence estimates for 16 majorcancers in Europe at the beginning of the year 2003.Patients and methods: We estimated complete prevalence by the completeness index method. We usedinformation on cancer patients diagnosed in 1978-2002 with vital status information available up to 31December 2003, from 76 European cancer registries.Results: About 11.6 millions of Europeans with a history of one of the major considered cancers were alive on1 January 2003. For breast and prostate cancers, about 1 out of 73 women and 1 out of 160 men were living with aprevious diagnosis of breast and prostate cancers, respectively. The demographic variations alone will increase thenumber of prevalent cases to nearly 13 millions in 2010.Conclusions: Several factors (early detection, population aging and better treatment) contribute to increase cancerprevalence and push for the need of a continuous monitoring of prevalence indicators to properly plan needs, resourceallocation to cancer and for improving health care programs for cancer survivors. Cancer prevalence should beincluded within the EU official health statistics. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

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