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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. Source

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. Source

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. Source

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. Source

Sant M.,Analytical Epidemiology and Health Impact Unit | Minicozzi P.,Analytical Epidemiology and Health Impact Unit | Mounier M.,University of Burgundy | Anderson L.A.,Queens 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. Source

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