Netherlands Cancer Registry Data Research Articles

Medical costs of lung cancer by stage, histology and first-line treatment modality in the Netherlands (2012–2021)

IntroductionLung cancer is a leading cause of mortality worldwide, with lung cancer treatment presenting a significant financial burden. The treatment landscape has recently shifted, seeing an increase in targeted- and immunotherapies. Such treatments are expensive, but estimates of the medical costs of the lung cancer treatment pathway largely predate their introduction. MethodsWe link medical expenditures of individuals resident in the Netherlands (n = 19.2 m) for 2013–2021 to tumour-level (n = 137,129, incident 2012–2021) Netherlands Cancer Registry data. We estimate lung cancer-attributable costs by phase of care (initial, continuing and terminal), stratified by cancer stage and histology, and observe trends in medical costs over time. ResultsWe estimate mean costs over the lung cancer treatment pathway to be €48,443 per patient. Total medical costs are highest in the initial phase, followed by the terminal and continuing phase. Monthly treatment for stage IV lung cancer is significantly more expensive than for early-stage disease (€8293 per month of initial care relative to €3228 for stage IA). Stage IV lung cancer has become significantly more expensive to treat 2018–2021 relative to 2013–2017, with monthly expenditures rising 55 % in initial care and 148 % in continuing care. Population-wide, we find €900.6 million spent on lung cancer care in 2021, €433 million more than in 2016, of which €307.3 million is attributed to per-patient expenditure trends. ConclusionsTreatment advances are quickly inflating medical costs for late-stage lung cancer. Policy makers should carefully evaluate the cost-effectiveness of novel treatments, and incorporate stage-specific treatment costs in evaluating interventions for early detection.

Development of machine learning models to predict cancer-related fatigue in Dutch breast cancer survivors up to 15 years after diagnosis

Abstract Purpose To prevent (chronic) cancer-related fatigue (CRF) after breast cancer, it is important to identify survivors at risk on time. In literature, factors related to CRF are identified, but not often linked to individual risks. Therefore, our aim was to predict individual risks for developing CRF. Methods Two pre-existing datasets were used. The Nivel-Primary Care Database and the Netherlands Cancer Registry (NCR) formed the Primary Secondary Cancer Care Registry (PSCCR). NCR data with Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship (PROFILES) data resulted in the PSCCR-PROFILES dataset. Predictors were patient, tumor and treatment characteristics, and pre-diagnosis health. Fatigue was GP-reported (PSCCR) or patient-reported (PSCCR-PROFILES). Machine learning models were developed, and performances compared using the C-statistic. Results In PSCCR, 2224/12813 (17%) experienced fatigue up to 7.6 ± 4.4 years after diagnosis. In PSCCR-PROFILES, 254 (65%) of 390 patients reported fatigue 3.4 ± 1.4 years after diagnosis. For both, models predicted fatigue poorly with best C-statistics of 0.561 ± 0.006 (PSCCR) and 0.669 ± 0.040 (PSCCR-PROFILES). Conclusion Fatigue (GP-reported or patient-reported) could not be predicted accurately using available data of the PSCCR and PSCCR-PROFILES datasets. Implications for Cancer Survivors CRF is a common but underreported problem after breast cancer. We aimed to develop a model that could identify individuals with a high risk of developing CRF, ideally to help them prevent (chronic) CRF. As our models had poor predictive abilities, they cannot be used for this purpose yet. Adding patient-reported data as predictor could lead to improved results. Until then, awareness for CRF stays crucial.

Outcome of Intensively Treated Elderly AML Patients Reported to the Harmony Alliance Compares Well to Outcome of Control Patients of the Prospective Randomized HOVON 103 Study in Elderly AML

Introduction: The evaluation of novel drugs in hemato-oncology is hampered by relatively large sample sizes needed for sufficiently powered, randomized controlled trials (RCT). External control data are increasingly applied in prospective phase II and III studies, and might be derived from Real-World Data (RWD) sources, such as national cancer registries. The HARMONY Alliance recently reported on a big data platform, consisting of data that were generated by cooperative European acute myeloid leukemia (AML) study groups ( Lang et al., Trials, 2020). HARMONY or cancer registry data might supplement prospectively collected trial control data. Here, we investigated whether and to what extent data included in the HARMONY AML database and RWD from the Netherlands Cancer Registry (NCR) compare to the control arm of the recently reported prospective randomized HOVON-103 (H103) study in elderly AML ( Ossenkoppele et al., Leukemia, 2020; Janssen et al., Leukemia, 2022). Methods: The H103 trial consecutively randomized newly diagnosed AML patients aged >65 years between standard induction chemotherapy with or without lenalidomide, tosedostat, or selinexor. External control patients concerned newly diagnosed (HARMONY: 2010-2018; NCR: 2014-2018) and intensively treated (intensified cytarabine/anthracycline) elderly AML patients aged >60 years. H103 were matched 1:1 using nearest neighbor propensity scores with NCR and HARMONY patients for age, European Leukemia Net (ELN) 2022 risk classification, and leukocyte count at diagnosis, while HARMONY patients were additionally matched for WHO performance score. Patients with missing values for propensity score factors were excluded from that analysis. The primary endpoint was overall survival (OS), calculated by the Kaplan-Meier method. Results: 67% of HARMONY patients (n=510) concerned trial patients. Median age was lower for HARMONY patients compared with H103-controls (n=279) (67 vs. 69 years, P<0.01), with also a preponderance of male patients in the H103 cohort (54% vs. 62%, P=0.03). Age and male sex did not differ between H103-controls and NCR patients (n=320) (69 vs. 69 years, P=0.46; 62% vs. 62%, P=1.0) (Table 1). WHO performance score of 0 or 1 was reported in 49% and 41% of H103-controls which was less frequent in HARMONY and NCR data (8% and 31%, P<0.01; 26% and 18%, P<0.01, respectively). Unknown WHO status was more prevalent in the external cohorts than in H103, at 43%, 54%, and 1% for the HARMONY, NCR, and H103 cohorts, respectively. ELN 2022 risk (favorable vs. non-favorable) was reported in 24% vs. 76% of H103 patients, which was similar in HARMONY patients (26% vs. 74%; P=0.73). ELN 2022 risk differed, however, for NCR patients (17% vs 83%; P=0.03). The median leukocyte count at diagnosis was lower for H103-controls than for HARMONY and NCR patients (3.65 vs. 17.1, P<0.01; 3.65 vs. 13.1, P<0.01, respectively). Propensity scores matched 278 HARMONY patients and 278 NCR patients to H103-controls. The 2-year OS (estimate±SE) was 40±3% for H103-controls vs. 35±3% for HARMONY patients (P=0.22), and vs. 30±3% for NCR patients (P=0.052), respectively (Figure 1). Conclusion: Characteristics of H103-controls and HARMONY patients appeared largely comparable, while NCR patients were more frequently ELN 2022 non-favorable risk. Following matching, OS was similar between H103-controls and HARMONY patients, while NCR patients showed inferior OS. The inclusion of a large proportion of trial patients in the HARMONY cohort, adhering to strict inclusion and exclusion criteria and fewer comorbidities compared to RWD patients, might explain these observations. These results suggest that matched data of the HARMONY Alliance might supplement prospectively collected control data in studies evaluating intensive therapy in elderly AML.

A novel method for continuous measurements of clinical practice guideline adherence.

Clinical practice guidelines (hereafter 'guidelines') are crucial in providing evidence-based recommendations for physicians and multidisciplinary teams to make informed decisions regarding diagnostics and treatment in various diseases, including cancer. While guideline implementation has been shown to reduce (unwanted) variability and improve outcome of care, monitoring of adherence to guidelines remains challenging. Real-world data collected from cancer registries can provide a continuous source for monitoring adherence levels. In this work, we describe a novel structured approach to guideline evaluation using real-world data that enables continuous monitoring. This method was applied to endometrial cancer patients in the Netherlands and implemented through a prototype web-based dashboard that enables interactive usage and supports various analyses. The guideline under study was parsed into clinical decision trees (CDTs) and an information standard was drawn up. A dataset from the Netherlands Cancer Registry (NCR) was used and data items from both instruments were mapped. By comparing guideline recommendations with real-world data an adherence classification was determined. The developed prototype can be used to identify and prioritize potential topics for guideline updates. CDTs revealed 68 data items for recording in an information standard. Thirty-two data items from the NCR were mapped onto information standard data items. Four CDTs could sufficiently be populated with NCR data. The developed methodology can evaluate a guideline to identify potential improvements in recommendations and the success of the implementation strategy. In addition, it is able to identify patient and disease characteristics that influence decision-making in clinical practice. The method supports a cyclical process of developing, implementing and evaluating guidelines and can be scaled to other diseases and settings. It contributes to a learning healthcare cycle that integrates real-world data with external knowledge.

External validation of 87 clinical prediction models supporting clinical decisions for breast cancer patients.

Numerous prediction models have been developed to support treatment-related decisions for breast cancer patients. External validation, a prerequisite for implementation in clinical practice, has been performed for only a few models. This study aims to externally validate published clinical prediction models using population-based Dutch data. Patient-, tumor- and treatment-related data were derived from the Netherlands Cancer Registry (NCR). Model performance was assessed using the area under the receiver operating characteristic curve (AUC), scaled Brier score, and model calibration. Net benefit across applicable risk thresholds was evaluated with decision curve analysis. After assessing 922 models, 87 (9%) were included for validation. Models were excluded due to an incomplete model description (n=262 (28%)), lack of required data (n=521 (57%)), previously validated or developed with NCR data (n=45 (5%)), or the associated NCR sample size was insufficient (n=7 (1%)). The included models predicted survival (33 (38%) overall, 27 (31%) breast cancer-specific, and 3 (3%) other cause-specific), locoregional recurrence (n=7 (8%)), disease free survival (n=7 (8%)), metastases (n=5 (6%)), lymph node involvement (n=3 (3%)), pathologic complete response (n=1 (1%)), and surgical margins (n=1 (1%)). Seven models (8%) showed poor (AUC<0.6), 39 (45%) moderate (AUC:0.6-0.7), 38 (46%) good (AUC:0.7-0.9), and 3 (3%) excellent (AUC≥0.9) discrimination. Using the scaled Brier score, worse performance than an uninformative model was found in 34 (39%) models. Comprehensive registry data supports broad validation of published prediction models. Model performance varies considerably in new patient populations, affirming the importance of external validation studies before applying models in clinical practice. Well performing models could be clinically useful in a Dutch setting after careful impact evaluation.

Trajectories of cognitive symptoms and associated factors in cancer survivors after return to work: an 18-month longitudinal cohort study

PurposeCognitive symptoms affect cancer survivors’ functioning at work. To date, cognitive symptoms trajectories in working cancer survivors and the factors associated with these trajectories have not been examined.MethodsData from a heterogeneous group of working cancer survivors (n = 379) of the longitudinal “Work-Life-after-Cancer” study, linked with Netherlands Cancer Registry data, were used. The Cognitive Symptom Checklist-Work was administered at baseline (within the first 3 months after return to work), 6-, 12-, and 18-month follow-up to measure self-perceived memory and executive function symptoms. Data were analyzed using group-based trajectory modeling.ResultsFour trajectories of memory and executive function symptoms were identified. All memory symptoms trajectories were stable and labeled as “stable-high” (15.3% of the sample), “stable-moderately high” (39.6%), “stable-moderately low” (32.0%), and “stable-low” (13.0%). Executive function symptoms trajectories changed over time and were labeled as “increasing-high” (10.1%), “stable-moderately high” (32.0%), “decreasing-moderately low” (35.5%), and “stable-low” (22.4%). Higher symptoms trajectories were associated with older age, longer time from diagnosis to return to work, more quantitative work demands, and higher levels of depressive symptoms at baseline.ConclusionsIn cancer survivors who returned to work, four cognitive symptoms trajectory subgroups were identified, representing different but relatively stable severity levels of cognitive symptoms.Implications for Cancer SurvivorsTo identify cancer survivors with higher symptoms trajectories, health care providers should assess cognitive symptoms at baseline after return to work. In case of cognitive symptoms, it is important to also screen for psychological factors to provide appropriate guidance.

Age and prognosis in patients with pancreatic cancer: a population-based study

Background The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged <60 years to older PDAC patients. Method This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015–31 December 2018). Kaplan–Meier curves and Cox proportional hazards models were used to assess OS. Results Overall, 10,298 patients were included, of whom 1551 (15%) were <60 years. Patients <60 years were more often male, had better performance status, less comorbidities and less stage I disease, and more often received anticancer treatment (67 vs. 33%, p < 0.001) than older patients. Patients <60 years underwent resection of the tumour more often (22 vs. 14%p < 0.001), more often received chemotherapy, and had a better median OS (6.9 vs. 3.3 months, p < 0.001) compared to older patients. No differences in median OS were demonstrated between both age groups of patients who underwent resection (19.7 vs. 19.4 months, p = 0.123), received chemotherapy alone (7.8 vs. 8.5 months, p = 0.191), or received no anticancer treatment (1.8 vs. 1.9 months, p = 0.600). Patients <60 years with stage-IV disease receiving chemotherapy had a somewhat better OS (7.5 vs. 6.3 months, p = 0.026). Conclusion Patients with PDAC <60 years more often underwent resection despite less stage I disease and had superior OS. Stratified for treatment, however, survival was largely similar.

Age-group-specific trend analyses of oropharyngeal squamous cell carcinoma incidence from 1989 to 2018 and risk factors profile by age-group in 2015-2018: a population-based study in The Netherlands.

Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally and the human papillomavirus (HPV) has been linked to this increase. This study aimed to present a comprehensive overview of OPSCC trends in incidence rates by age group and investigate differences in risk factors profile. Netherlands Cancer Registry data from 1989-2018 were analyzed to calculate the annual percentage change (APC) over European standardized incidence rates by gender and age group using joinpoint regression software. Smoking, alcohol drinking and HPV-status were available for 2015-2018. During 1989-2018, 13 048 cases of OPSCC were reported with a male-to-female ratio of 2.1:1. The overall incidence rate increased by 5.4% (APC) annually from 1989 to 1996 but slowed thereafter by 1.2%. Significant declines were found in patients of 35-44 years (APCs -3.7%). Adults aged 45-59 years displayed significant increases from 1989 to 2001, followed by a significant decline. In patients ≥60 years, the incidence rates increased overall, with APC for women being consistently higher than men. The data on HPV status was available for 69% of the patients, of whom 47% were HPV+. Smoking and alcohol consumption were more prevalent, that is 75 and 76 % respectively. The declining trends of OPSCC for Dutch people aged 35-44 years from 1989 to 2018 and for those aged 45-59 years from 2002 onwards are inconsistent to trends reported elsewhere in the developed countries. The prevalence of smoking and drinking alcohol was quite high in all age groups, whereas the proportion of HPV-positivity was relatively low.

Prophylactic cranial irradiation in patients with small cell lung cancer in The Netherlands: A population-based study

IntroductionControversy has arisen regarding the benefit of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC), particularly since the 2017 Takahashi trial publication that supports MRI surveillance in extensive-stage (ES-)SCLC. The primary aim of this study was to assess trends and determinants in PCI use over the years 2010–2018. A secondary aim was to determine contemporary practice considerations among radiation oncologists (ROs). MethodsA nationwide population-based cohort study was conducted using the Netherlands Cancer Registry data on all newly diagnosed SCLC patients (2010–2018). The change in PCI frequency over the years and determinants for PCI were analyzed using logistic regression models. Second, an online survey was performed among Dutch lung cancer ROs in 2020. ResultsAmong 10,264 eligible patients, 4,894 (47%) received PCI. Compared to 2010–2014, PCI use significantly decreased in 2017–2018 in ES-SCLC (OR 0.68, 95%CI 0.60–0.77) and LS-SCLC (OR 0.56, 95%CI 0.47–0.67). Incidence year, age, performance status, and thoracic radiotherapy were independent determinants for PCI. Among 41 survey participants, PCI was recommended always/sometimes/never by 22%/71%/7% in ES-SCLC and 54%/44%/2% in LS-SCLC. For ES-SCLC and LS-SCLC, 63% and 25% of ROs, respectively, confirmed influence of the Takahashi trial on PCI recommendations. Denial of such influence was associated with insufficient institutional MRI capacity. ConclusionsA significant declining trend of PCI use in both ES-SCLC and LS-SCLC was observed in The Netherlands since 2017. The Takahashi trial seems an explanation for this trend even in LS-SCLC, with differential influence of the trial depending on institutional MRI capacity. An alarming increase in practice variation regarding PCI was found which stresses the importance of ongoing trials.

Persistent Hematologic Dysfunction after Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE: Incidence, Course, and Predicting Factors in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent hematologic dysfunction (PHD) after PRRT with 177Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP NETs). Methods: The incidence and course of PHD were analyzed in 274 GEP NET patients from a group of 367 patients with somatostatin receptor-positive tumors. PHD was defined as diagnosis of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), MDS/MPN, or otherwise unexplained cytopenia (for >6 mo). Using data from The Netherlands Cancer Registry, the expected number of hematopoietic neoplasms (MDS, AML, MPN, and MDS/MPN) was calculated and adjusted for sex, age, and follow-up period. The following risk factors were assessed: sex, age over 70 y, bone metastasis, prior chemotherapy, prior external-beam radiotherapy, uptake on the [111In-DTPA0]octreotide scan, tumor load, grade 3-4 hematologic toxicity during treatment, estimated absorbed BM dose, elevated plasma chromogranin A level, baseline blood counts, and renal function. Results: Eleven (4%) of the 274 patients had PHD after treatment with 177Lu-DOTATATE: 8 patients (2.9%) developed a hematopoietic neoplasm (4 MDS, 1 AML, 1 MPN, and 2 MDS/MPN) and 3 patients (1.1%) developed BM failure characterized by cytopenia and BM aplasia. The median latency period at diagnosis (or first suspicion of a PHD) was 41 mo (range, 15-84 mo). The expected number of hematopoietic neoplasms based on The Netherlands Cancer Registry data was 3.0, resulting in a relative risk of 2.7 (95% confidence interval, 0.7-10.0). No risk factors for PHD could be identified for the GEP NET patients, not even bone metastasis or estimated BM dose. Seven patients with PHD developed anemia in combination with a rise in mean corpuscular volume. Conclusion: The prevalence of PHD after PRRT with 177Lu-DOTATATE was 4% in our patient population. The median time at which PHD developed was 41 mo after the first PRRT cycle. The relative risk for developing a hematopoietic neoplasm was 2.7. No risk factors were found for the development of PHD in GEP NET patients.

Adjuvant systemic therapy in early breast cancer: impact of guideline changes and clinicopathological factors associated with nonadherence at a nation-wide level.

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.

The use of medical claims to assess incidence, diagnostic procedures and initial treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia in the Netherlands

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) may be underreported in cancer registries such as the Netherlands Cancer Registry (NCR). Analysis of Dutch medical claims can complement NCR data on MDS and CMML. We analyzed data on 3681 MDS patients and 235 CMML patients aged ≥18 years with initial claims for MDS or CMML from the Dutch nationwide medical claims-based Diagnosis Treatment Combination Information System (DIS) between 2008 and 2010. Clinical information was available in the DIS. MDS and CMML were diagnosed without a bone marrow (BM) examination in almost half of the patients. The age-standardized incidence rate (ASR) per 100,000 in the cohort that underwent BM examinations compared with NCR data was 2.8 vs. 3.3 for MDS and 0.2 vs. 0.4 for CMML in 2008–2010. A conservative treatment approach was associated with increasing age and absence of BM examination in MDS (p<0.001 for both) and CMML patients (p<0.033 for both). In conclusion, the ASR of MDS in the cohort that underwent BM examinations was comparable with the NCR. The majority of elderly patients, either with or without BM examinations, received no therapy. Together, MDS and CMML may be misdiagnosed and inappropriately managed without a BM confirmation.

Increased risk of chronic lymphocytic leukaemia among cancer survivors in the Netherlands: increased detection, causal factors or both?

We assessed the risk of chronic lymphocytic leukaemia (CLL) following earlier primary malignancies (EPM) to explore the extent and determinants of this risk. We used the Netherlands Cancer Registry data of 1,313,232 cancer survivors who were at risk to be subsequently diagnosed with CLL between 1989 and 2008. Cancer survivors were categorized based on gender, age, time since diagnosis of EPM and type of EPM. CLL was regarded synchronous when diagnosed within 3 months after diagnosis of EPM; metachronous CLLs were those diagnosed later. Overall, we found that cancer survivors had a 90 % higher risk to be diagnosed with CLL than the general population. In the first year after diagnosis, we found a more than four-fold increased risk of CLL (standardized incidence ratio (SIR), 4.4; 95 % confidence interval (CI), 4.1-4.8); however, no increased risk was observed after excluding synchronous cases. After 1 year, the excess risk of subsequent CLL ranged from 1.2 to 1.8. An increased risk for metachronous CLL was found in prostate (SIR 1.3; 95 % CI 1.1-1.5) and squamous cell skin cancer survivors (SIR 2.3; 95 % CI 1.9-2.7). Intensive clinical checkups after/around diagnosis of the EPM seemed to be the main cause for the increased risk of CLL among cancer survivors. However, possible shared risk factors between prostate cancer and CLL and skin cancer and CLL cannot be excluded. Further clinical research aimed at CLL as subsequent primary malignancy (SPM) is warranted to elucidate possible shared biological and predisposing risk factors.

P2-160 Right-side shifting of second colorectal cancer-implications for aetiology and clinical relevance

BackgroundColorectal cancer (CRC) is a heterogeneous disease: cancers in proximal, distal colon and rectum show differences in carcinogenesis pathways (proximal colon cancer related to microsatellite instability vs distal colon cancer...

Does Specialized Care Improve Ovarian Cancer Outcomes

Previous studies have indicated that women with ovarian cancer survive longer when care is provided at specialized rather than general hospitals. To assess disease-specific survival by type of hospital providing treatment, investigators conducted a retrospective cohort study linking Netherlands Cancer Registry data for 8621 Dutch women diagnosed with ovarian cancer from 1996 through 2003 to national mortality …