Netherlands Cancer Registry Research Articles

Incidence and survival of paediatric renal tumours in the Netherlands between 1990 and 2014

BackgroundThis population-based study is the first to provide a detailed analysis of trends in incidence and survival of children and adolescents diagnosed with renal malignancies in the Netherlands. MethodsData on all renal malignancies diagnosed in paediatric patients (0–18 years) between 1990 and 2014 [N = 648, 92% Wilms tumour (WT)] were extracted from the Netherlands Cancer Registry. Five-year overall survival (OS) was estimated using the actuarial method. Time trends in incidence were assessed by calculating average annual percentage change. A parametric survival model was used to compare the multivariable-adjusted risk of dying from WT between two diagnostic periods. ResultsThe incidence was 8 per million person-years and was constant over time (average annual percentage change -0.8%, p = 0.29). Patients with WT had a favourable outcome in both time periods; 5-year OS was 88% in 1990–2001 and 91% in 2002–2014. Multivariable analysis showed that the risk of dying from WT was not significantly decreased in the latest period (hazard ratio, 95% CI: 0.7, 0.4–1.3). Five-year OS decreased with increasing disease stage, ranging from 95 to 100% for stage I-II and about 80% for stage III–IV to 74% for bilateral disease. Five-year OS were 81% for renal cell carcinoma, 77% for clear cell sarcoma of the kidney and 20% for malignant rhabdoid tumour of the kidney. ConclusionsIncidence of paediatric renal malignancies in the Netherlands has been stable since the 1990s. Five-year OS of WT reached 91% and was similar to findings for other developed countries. Contrary to the excellent outcome for WT, the outcome of malignant rhabdoid tumour of the kidney remained inferior.

Risk of metachronous contralateral breast cancer in patients with primary invasive lobular breast cancer: Results from a nationwide cohort.

Lobular primary breast cancer (PBC) histology has been proposed as a risk factor for contralateral breast cancer (CBC), but results have been inconsistent. We investigated CBC risk and the impact of systemic therapy in lobular versus ductal PBC. Further, CBC characteristics following these histologic subtypes were explored. We selected 74,373 women diagnosed between 2003 and 2010 with stage I-III invasive PBC from the nationwide Netherlands Cancer Registry. We assessed absolute risk of CBC taking into account competing risks among those with lobular (n= 8903), lobular mixed with other types (n= 3512), versus ductal (n= 62,230) histology. Hazard ratios (HR) for CBC were estimated in a cause-specific Cox model, adjusting for age at PBC diagnosis, radiotherapy, chemotherapy and/or endocrine therapy. Multivariable HRs for CBC were 1.18 (95% CI: 1.04-1.33) for lobular and 1.37 (95% CI: 1.16-1.63) for lobular mixed versus ductal PBC. Ten-year cumulative CBC incidences in patients with lobular, lobular mixed versus ductal PBC were 3.2%, 3.6% versus 2.8% when treated with systemic therapy and 6.6%, 7.7% versus 5.6% in patients without systemic therapy, respectively. Metachronous CBCs were diagnosed in a less favourable stage in 19%, 26% and 23% and less favourable differentiation grade in 22%, 33% and 27% than the PBCs of patients with lobular, lobular mixed and ductal PBC, respectively. In conclusion, lobular and lobular mixed PBC histology are associated with modestly increased CBC risk. Personalised CBC risk assessment needs to consider PBC histology, including systemic treatment administration. The impact on prognosis of CBCs with unfavourable characteristics warrants further evaluation.

KS04.6.A Epidemiology of adult meningioma in the Netherlands: a population-based study

Abstract Background Meningiomas are the most common primary tumours of the central nervous system. As the majority of meningiomas are benign, initial management often consists of observation only. Consequently, estimates on meningioma incidence are generally considered too low, with many registries mainly depending on pathology notifications. With additional notification sources, this study provides more complete population-based estimates on the incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands. Material and Methods Data on patients diagnosed with meningioma during 2000-2019 were obtained from the Netherlands Cancer Registry (NCR), which was expanded to the Dutch Brain Tumour Registry (DBTR) for meningiomas as of 2016. In addition to histological confirmations, the NCR/DBTR receives case notifications from hospital administrative registrations on cost reimbursement and outpatient care. In addition, a data linkage was performed with a clinical database maintained by one of the Dutch neuro-oncology centres to evaluate local completeness of the NCR/DBTR. Time trends of the age-adjusted incidence rates were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar-Perme estimator. Results From 2000 to 2019, a total of 22,605 cases of meningioma were registered; 11,423 (50.5%) were histologically confirmed, while 11,182 (49.5%) had a radiological diagnosis. Over time, incidence increased from 4.7 per 100,000 inhabitants (European Standardized Rate, ESR) to 10.7 (EAPC 4.6%, p<0.01); the incidence of radiological diagnosis increased from 1.2 to 6.9 per 100,000 ESR (EAPC 9.6%, p<0.01). Local data completeness was estimated at 98% for histologically confirmed meningiomas and 87% for radiological diagnoses. On the basis of these incidence estimates, the prevalence of meningioma is estimated at 105/100,000 on January 1st of 2020, with over 17,500 individuals having had a diagnosis of meningioma at that moment. Relative survival rate at 5 years for grade I meningiomas was 94.8% (95%-confidence interval: 94.0%-95.4%), 84.0% (95%CI: 81.0%-86.5%) for grade II meningiomas, and 47.3% (95%CI: 38.2%-55.8%) for grade III meningiomas. Conclusion As the incidence estimates in this study may be considered most complete, the results obtained should approximate the true incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands.

Breast cancer mortality of older patients with and without recurrence analysed by novel multi-state models

IntroductionIn older patients with breast cancer, the risk of dying from other causes than breast cancer strongly increases after the age of 70. The aim of this study was to assess contributions of breast cancer mortality versus other-cause mortality after locoregional or distant recurrence in a population-based cohort of older patients analysed by multi-state models. MethodsSurgically treated patients ≥70 years diagnosed with stage I-III breast cancer in 2003–2009 were selected from the Netherlands Cancer Registry. A novel multi-state model with locoregional and distant recurrence that incorporates relative survival was fitted. Other-cause and breast cancer mortality were indicated as population and excess mortality. ResultsOverall, 18,419 patients were included. Ten-year cumulative incidences of locoregional and distant recurrence were 2.8% (95%CI 2.6–3.1%) and 12.5% (95%CI 11.9–13.1%). Other-cause mortality increased from 23.9% (95%CI 23.7–24.2%) in patients 70–74 years to 73.8% (95%CI 72.2–75.4%) in those ≥80 years. Ten-year probabilities of locoregional or distant recurrence with subsequent breast cancer death were 0.4–1.3% and 10.2–14.6%, respectively. For patients with a distant recurrence in the first two years after diagnosis, breast cancer death probabilities were 95.3% (95%CI 94.2–96.4%), 93.1% (95%CI 91.6–94.6%), and 88.6% (95%CI 86.5–90.8%) in patients 70–74, 75–79, and ≥80 years. ConclusionIn older patients without recurrence, prognosis is driven by other-cause mortality. Although locoregional recurrence is a predictor for worse outcome, given its low incidence it contributes little to breast cancer mortality after diagnosis. For patients who develop a distant recurrence, breast cancer remains the dominant cause of death, even at old age.

364P Prevalence, treatment and survival of NTRK gene fusions in microsatellite instable metastatic colorectal cancer patients

TRK inhibitors are a treatment option for patients with NTRK fusions positive tumors, including metastatic colorectal cancer (mCRC). However, the clinical behavior, including response to standard therapy and overall survival, in NTRK fusion positive mCRC is unknown which complicates the interpretation of tumor agnostic basket trials studying TRK inhibitors. We aim to estimate the prevalence of NTRK fusions in microsatellite instable (MSI) mCRC and to determine patient characteristics and clinical behavior of this NTRK fusion subtype. FFPE tissue was requested from all MSI mCRC patients diagnosed between 2015 and 2020 in the Netherlands. Pan-Trk immunohistochemistry was used as screening method. Positive cases were analyzed by RNA-based NGS with Archer or FFPE-targeted locus capture to assess NTRK1, 2, and 3 rearrangements. Clinical data were retrieved from the Netherlands Cancer Registry. In total, 8 out of 203 tumors (3,9%) harbored an NTRK fusion: 7 rearrangements were found in the NTRK1 gene and 1 NTRK3-ETV6 fusion was detected. All NTRK-fusion positive tumors were RAS and BRAF wild-type. In the subgroup (n = 26) of RAS and BRAF wild-type MSI patients, prevalence of NTRK fusions was 23%. All NTRK-fusion positive tumors showed loss of MLH1 and PMS2 and MLH1 promotor hypermethylation was found in 7 out of 8 tumors. Benefit from chemotherapy (1/6) or anti-EGFR therapy (0/2) in NTRK-fusion positive patients was limited, but all four immunotherapy-treated patients had ongoing responses and a minimum overall survival of 470 days. The four patients who did not receive immunotherapy had a short overall survival (range 11-282 days). In this population wide cohort study, NTRK fusions are most prevalent (23%) in RAS and BRAF wild-type MSI mCRC patients. This is the first study to suggest resistance to chemotherapy and anti-EGFR therapy in NTRK-fusion positive tumors leading to impaired overall survival. In contrast, immunotherapy seems to be effective in NTRK-fusion positive patients. The clinical condition of the patient probably dictates the choice of upfront immunotherapy versus TRK inhibitors in this subgroup. We recommend early testing for NTRK fusions in RAS and BRAF wild-type MSI patients.

Treatment and overall survival of four types of non-metastatic periampullary cancer: nationwide population-based cohort study.

Periampullary adenocarcinoma consists of pancreatic adenocarcinoma (PDAC), distal cholangiocarcinoma (DC), ampullary cancer (AC), and duodenal adenocarcinoma (DA). The aim of this study was to assess treatment modalities and overall survival by tumor origin. Patients diagnosed with non-metastatic periampullary cancer in 2012-2018 were identified from the Netherlands Cancer Registry. OS was studied with Kaplan-Meier analysis and multivariable Cox regression analyses, stratified by origin. Among the 8758 patients included, 68% had PDAC, 13% DC, 12% AC, and 7% DA. Resection was performed in 35% of PDAC, 56% of DC, 70% of AC, and 59% of DA. Neoadjuvant and/or adjuvant therapy was administered in 22% of PDAC, 7% of DC, 7% of AC, and 12% of DA. Three-year OS was highest for AC (37%) and DA (34%), followed by DC (21%) and PDAC (11%). Adjuvant therapy was associated with improved OS among PDAC (HR=0.62; 95% CI 0.55-0.69) and DC (HR=0.69; 95% CI 0.48-0.98), but not AC (HR=0.87; 95% CI 0.62-1.22) and DA (HR=0.85; 95% CI 0.48-1.50). This retrospective study identified considerable differences in treatment modalities and OS between the four periampullary cancer origins in daily clinical practice. An improved OS after adjuvant chemotherapy could not be demonstrated in patients with AC and DA.

Population-based study of treatment and outcome of recurrent oesophageal or junctional cancer.

Patients with cancer of the oesophagus or gastro-oesophageal junction have a high risk of recurrence after treatment with curative intent. The aim of this study was to analyse the site of recurrence, treatment, and survival in patients with recurrent disease. Patients with non-metastatic oesophageal or junctional carcinoma treated with curative intent between January 2015 and December 2016 were selected from the Netherlands Cancer Registry. Data on recurrence were collected in the second half of 2019. Overall survival (OS) was assessed by Kaplan-Meier methods. In total, 862 of 1909 patients (45.2 per cent) for whom information on follow-up was available had disease recurrence, and 858 patients were included. Some 161 of 858 patients (18.8 per cent) had locoregional recurrence only, 415 (48.4 per cent) had distant recurrence only, and 282 (32.9 per cent) had combined locoregional and distant recurrence. In all, 518 of 858 patients (60.4 per cent) received best supportive care only and 315 (39.6 per cent) underwent tumour-directed therapy. Patients with locoregional recurrence alone more often received chemoradiotherapy than those with distant or combined locoregional and distant recurrence (19.3 per cent versus 0.7 and 2.8 per cent), and less often received systemic therapy (11.2 per cent versus 30.1 and 35.8 per cent). Median OS was 7.6, 4.2, and 3.3 months for patients with locoregional, distant, and combined locoregional and distant recurrence respectively (P < 0.001). Disease recurred after curative treatment in 45.2 per cent of patients. Locoregional recurrence developed in only 18.8 per cent. The vast majority of patients presented with distant or combined locoregional and distant recurrence, and received best supportive care.

Limited impact of the COVID-19 pandemic on colorectal cancer care in the Netherlands in 2020

PurposeThe COVID-19 pandemic had a major impact on the health services worldwide. We aimed to investigate the impact of the pandemic on colorectal cancer (CRC) care in the Netherlands in 2020.MethodsCRC patients, diagnosed in 2018–2020 in the Netherlands, were selected from the Netherlands Cancer Registry (NCR). The year 2020 was divided in four periods reflecting COVID-19 developments in the Netherlands (pre-COVID, 1st peak, recovery period, 2nd peak) and compared with the same periods in 2018/2019. Patient characteristics and treatment were compared using the Chi-squared test. Median time between diagnosis and treatment, and between (neo)adjuvant therapy and surgery were analyzed by the Mann–Whitney U test.ResultsIn total, 38,021 CRC patients were diagnosed in 2018/2019 (n = 26,816) and 2020 (n = 11,205). Median time between diagnosis and initial treatment decreased on average 4 days and median time between neoadjuvant radiotherapy and surgery in clinical stage II or III rectal cancer patients increased on average 34 days during the three COVID-19 periods compared to the same periods of 2018/2019. The proportion of colon cancer patients that underwent elective surgery significantly decreased with 3.0% during the 1st peak. No differences were found in the proportion of patients who received (neo)adjuvant therapy, systemic therapy, or no anti-cancer treatment.ConclusionOnly minor changes in the care for CRC patients occurred during the COVID-19 pandemic, mostly during the 1st peak. In conclusion, the impact on CRC care in the Netherlands was found to be limited. However, long-term effects cannot be precluded.

Prognostic factors among patients with brain metastases from cancer of unknown primary site.

Cancers of an unknown primary site (CUPs) have a dismal prognosis, and the situation is even worse for CUPs patients withbrain metastases (BM-CUPs). This study aims to give better insight into the occurrence and survival of BM-CUPs patients. Cases were selected from the Netherlands Cancer Registry (1,430 BM-CUPs/17,140 CUPs). Baseline characteristics between CUPs patients with and without BM were tested using chi-square tests and Mann-Whitney U tests. Patients' overall survival (OS) times were estimated by the Kaplan-Meier method and prognostic factors on OS was assessed using Cox proportional hazards regression analyses. The proportion of BM-CUPs patients among CUPs increased from 8% in 2009-2010 to 10% in 2017-2018 (p < 0.001). Most patients presented with multiple brain lesions (53%). Survival of BM-CUPs improved over time: one-year OS increased from 10% for patients diagnosed in 2009-2010 to 17% (2017- 2018) (p < 0.01), and median survival times increased from 1.8months to 2.2months. Independent predictors of poor survival were multiple (HR 1.25; p < 0.01) or unknown (HR 1.48; p < 0.01) locations of BM, unknown/poorly/undifferentiated carcinoma histology (HR 1.53; p < 0.01), or clinical symptoms of BM (HR 1.74; p < 0.01), accompanying liver metastasis (HR 1.43; p < 0.01) and more than one metastatic site outside the brain compared to none (HR 1.52; p < 0.01). The incidence of patients with BM-CUPs is steadily increasing over time and overall prognosis remains dismal. Our results, however, show distinct patient subgroups that exhibit comparatively better outcomes, and more predictors may likely still be identified.

Long-Term Oncological Outcomes After Colorectal Anastomotic Leakage: A Retrospective Dutch Population-based Study.

Objective:The aim was to evaluate the impact of anastomotic leak (AL) after colon cancer (CC) and rectal cancer (RC) surgery on 5-year relative survival, disease-free survival (DFS), and disease recurrence.Background:AL after CC and RC resection is a severe postoperative complication with conflicting evidence whether it deteriorates long-term outcomes.Methods:Patients with stage I to IV CC and RC who underwent resection with primary anastomosis were included from the Netherlands Cancer Registry (2008–2018). Relative survival, measured from day of resection, and multivariable relative excess risks (RERs) were analyzed. DFS and recurrence were evaluated in a subset with stage I to III patients operated in 2015. All analyses were performed with patients who survived 90 days postoperatively.Results:A total of 65,299 CC and 22,855 RC patients were included. Five-year relative survival after CC resection with and without AL was 95% versus 100%, 89% versus 94%, 66% versus 76%, and 28% versus 25% for stage I to IV disease. AL was associated with a significantly higher RER for death in stage II and III CC patients. Stage-specific 5-year relative survival in RC patients with and without AL was 97% versus 101%, 90% versus 95%, 74% versus 83%, and 32% versus 41%. AL was associated with a significantly higher RER for death in stage III and IV RC patients. DFS was significantly lower in CC patients with AL, but disease recurrence was not associated with AL after colorectal cancer resection.Conclusion:AL has a stage-dependent negative impact on survival in both CC and RC, but no independent association with disease recurrence.

The influence of multidisciplinary team meetings on treatment decisions in advanced bladder cancer.

To investigate the role of specialised genitourinary multidisciplinary team meetings (MDTMs) in decision-making and identify factors that influence the probability of receiving a treatment plan with curative intent for patients with muscle invasive bladder cancer (MIBC). Data relating to patients with cT2-4aN0/X-1 M0 urothelial cell carcinoma, diagnosed between November 2017 and October 2019, were selected from the nationwide, population-based Netherlands Cancer Registry ('BlaZIB study'). Curative treatment options were defined as radical cystectomy (RC) with or without neoadjuvant chemotherapy, chemoradiation or brachytherapy. Multilevel logistic regression analyses were used to examine the association between MDTM factors and curative treatment advice and how this advice was followed. Of the 2321 patients, 2048 (88.2%) were discussed in a genitourinary MDTM. Advanced age (>80 years) and poorer World Health Organization performance status (score 1-2 vs 0) were associated with no discussion (P < 0.001). Being discussed was associated with undergoing treatment with curative intent (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.9-4.9), as was the involvement of a RC hospital (OR 1.70, 95% CI 1.09-2.65). Involvement of an academic centre was associated with higher rates of bladder-sparing treatment (OR 2.05, 95% CI 1.31-3.21). Patient preference was the main reason for non-adherence to treatment advice. For patients with MIBC, the probability of being discussed in a MDTM was associated with age, performance status and receiving treatment with curative intent, especially if a representative of a RC hospital was present. Future studies should focus on the impact of MDTM advice on survival data.

Peritoneal Metastases from Extraperitoneal Primary Tumors: Incidence, Treatment, and Survival from a Nationwide Database

The objective of this study was to assess the incidence, treatment, and survival of patients with synchronous peritoneal metastases (PM) from extraperitoneal primary tumors. A cohort was selected from the Netherlands Cancer Registry (NCR), in which all patients diagnosed with PM in 2017 and 2018 were screened for eligibility. The five most common primary extraperitoneal origins of PM were included for further analyses: lung, breast, urinary tract, and kidney cancer and malignant melanoma. Survival was investigated using log-rank test between different primary tumor locations. In total, 480 patients were diagnosed with synchronous PM from extraperitoneal origins. The proportion of patients with PM per extraperitoneal origin ranged between 0.1 and 1.1%, with the highest proportion in lung cancer patients. Of all patients, 234 (49%) received tumor-directed treatment and 246 (51%) received no tumor-directed treatment. Survival in patients with PM from lung, breast, urinary tract, and kidney cancer and malignant melanoma was 1.6 months, 15.7 months, 5.4 months, 3.4 months, and 2.1 months, respectively (p < 0.001). In this study, a small, although significant number of patients with extraperitoneal cancer developed PM. The reported survival in patients with PM ranged between 1.6 and 15.7 months. Only half of the patients with PM received tumor-directed treatment and survival in patients without tumor-directed treatment was only 1.2 months. These findings are stressing the need to explore new diagnostic tools that may enable earlier diagnosis of PM and may potentially lead to a more effective treatment.

Interlaboratory Gleason grading variation affects treatment: a Dutch historic cohort study in 30 509 patients with prostate cancer

AimSubstantial variation in Gleason grading (GG) of prostate cancer (PCa) exists between Dutch pathology laboratories. This study investigates its impact on treatment strategies.MethodsPathology reports of prostate needle biopsies and clinical...

Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival

BackgroundPathologic complete response (pCR) rates in early stage HER2-positive breast cancer improved after pertuzumab was added to neoadjuvant treatment. However, survival benefit is less-well established and seems mostly limited to node-positive patients. We used national cancer registry data to compare outcomes of patients treated with and without pertuzumab. MethodsWe identified stage II-III HER2-positive breast cancer patients treated with neoadjuvant trastuzumab-based chemotherapy between November 2013 until January 2016 from the Netherlands Cancer Registry. During that period pertuzumab was only available in the 37 hospitals that participated in the TRAIN-2 study. Missing grade and pCR-status were obtained from the Dutch Pathology Registry (PALGA) and cause of death from Statistics Netherlands. We used multiple imputation to impute missing data, multivariable logistic regression to evaluate the association between pertuzumab and pCR (ypT0/is, ypN0) and multivariable Cox regression models for overall survival and breast cancer specific survival (BCSS). ResultsWe identified 1124 patients of whom 453 received pertuzumab. Baseline characteristics were comparable, although tumor grade was missing more often in patients treated without pertuzumab (12% vs. 2%). Pertuzumab improved pCR rates (41% vs 65%, adjusted odds ratio [aOR] 2.91; 95% CI:2.20–3.94). After a median follow-up of 6.0 years, 5-year BCSS rates were 95% and 98% respectively (adjusted hazard ratio [aHR]: 0.58; 95% CI:0.36–0.95). Younger patients derived more benefit from pertuzumab, but no other significant interactions were found. ConclusionThese results support earlier data of a small survival benefit with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy which is most meaningful in younger patients.

Role of multidisciplinary team meetings in implementation of chemohormonal therapy in metastatic prostate cancer in daily practice.

The recommended treatment for a subset of patients with metastatic prostate cancer (mPC) changed from androgen deprivation therapy (ADT) to combinations with chemotherapy such as docetaxel. Implementation of new evidence from trials is however complex and challenging. We investigated the effect of multidisciplinary team meetings (MDTs) on adopting the newest emerging combination therapy in patients with mPC and assessed the overall survival of chemohormonal therapy in a real-world setting. All mPC patients diagnosed between October 2015 and April 2016 in the Netherlands were identified from the population-based Netherlands Cancer Registry (n = 962). Logistic regression analyses were performed to examine the role of patient- and tumor characteristics, with special emphasis on MDTs, on receiving chemohormonal therapy versus ADT monotherapy. Kaplan-Meier survival curves were used to assess overall survival (OS). As many patients received ADT monotherapy as chemohormonal therapy (both n = 452). Being discussed in a MDT as patient, younger age, less comorbidities, a better performance status and high-volume disease were significantly associated with receiving chemohormonal therapy compared to ADT monotherapy. After adjustment for these factors, the presence of a MDT was independently associated with the administration of chemohormonal therapy (OR 2.77, 95% CI 1.68-4.59). The 2-year OS was 82.1% (95% CI: 78.5-85.6%) for patients receiving chemohormonal therapy and 59.9% (95% CI: 55.4-64.4%) for patients receiving ADT monotherapy. Being discussed in a MDT is independently associated with the administration of chemohormonal therapy in this group of patients with mPC. This supports the hypothesis that implementation of innovative treatment options is facilitated by an organizational structure with MDTs.

Long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based study

BackgroundGastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) comprise a group of rare malignant tumours with heterogeneous behaviour. This study aimed to assess long-term survival and prognostic factors associated with survival, in order to optimise counselling. Patients and methodsThis population-based study included all GEP-NENs diagnosed between 1989 and 2016 in the Netherlands, selected from the Netherlands Cancer Registry. Overall survival (OS) and relative survival (RS) were calculated. A Cox Proportional Hazard analysis was used to identify prognostic factors (gender, age, tumour stage, location and treatment) for OS. Analyses were stratified by metastatic disease status and tumour grade. ResultsIn total, 9697 patients were included. In grade 1, 2 and 3 non-metastatic GEP-NENs (N = 6544), 5-year OS and RS were 81% and 88%, 78% and 83%, and 26% and 30%, respectively. In grade 1 non-metastatic GEP-NENs 10-year OS and RS were 68% and 83%. In grade 1, 2 and 3 metastatic GEP-NENs (N = 3153), 5-year OS and RS rates were 47% and 52%, 38% and 41%, and 5% and 5%, respectively. The highest (relative) survival rates were found in appendicular and rectal NENs, demonstrating 10-year OS and RS of 87% and 93%, and 81% and 95%, respectively. ConclusionsThese long-term follow-up data demonstrate significant differences in survival for different grades, tumour stage, and primary origin of GEP-NENs, with the most favourable overall and RS rates in patients with non-metastatic grade 1 appendicular and rectal NENs. This study demonstrates unique long-term OS and RS rates using combined stratification by tumour site, grade and stage.

Estimating Quality of Life Decrements in Oncology Using Time to Death

ObjectivesThe estimation of lifetime quality-adjusted life-years (QALYs) requires the extrapolation of both length and quality of life (QoL). The extrapolation of QoL has received little attention in the literature. Here we explore the predictive value of “time to death” (TTD) for extrapolating QoL in oncology. MethodsWe used QoL and survival data from the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry, which is linked to The Netherlands Cancer Registry. QoL was assessed with EQ-5D and SF-6D. We tested the relationship between TTD and QoL using linear, 2-part, and beta regression models. Incremental QALYs were compared using the TTD approach and an annual age-related disutility approach using artificial survival data with varying mortality rates. ResultsA total of 6 samples with >100 patients each were used for the analysis. A declining pattern in QoL was observed when patients were closer to death, confirming the predictive value of TTD for QoL. The declining pattern in QoL was most pronounced when QoL was measured with SF-6D. Proximity to death had a larger impact on QoL than age. Incremental QALYs were higher using the TTD approach than annual age-related disutility, ranging from +0.139 to +0.00003 depending on mortality rates. ConclusionsTTD is a predictor variable for QoL. Using TTD allows cost-effectiveness models that lack QoL data to extrapolate morbidity using overall survival estimates. The TTD approach generates more incremental QALYs than an annual age-related disutility, most notably for longer survival periods.

Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry

PurposeBladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy).MethodsA retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses.ResultsA total of 3484 patients were diagnosed with non-advanced MIBC in 2018–2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant.ConclusionsConsiderable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient’s sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes.

Short- and long-term impact of cancer on employment and financial outcomes of adolescents and young adults (AYAs): a large population-based case-control registry study in the Netherlands

Adolescent and young adult (AYA) cancer survivors, 18-39 years at initial cancer diagnosis, often self-report negative consequences of cancer (treatment) for their career. Less is known, however, about the objective impact of cancer on employment and financial outcomes. This study examines the employment and financial outcomes of AYA cancer survivors with nationwide population-based registry data and compares the outcomes of AYAs with cancer with an age- and sex-matched control population at year of diagnosis, 1 year later (short-term) and 5 years later (long-term). A total of 2527 AYAs, diagnosed in 2013 with any invasive tumor type and who survived for 5 years, were identified from the Netherlands Cancer Registry (clinical and demographic data) and linked to Statistics Netherlands (demographic, employment and financial data). AYAs were matched 1 : 4 with a control population based on age and sex (10 108 controls). Analyses included descriptive statistics, chi-square tests, independent samples t-tests, McNemar tests and logistic regression. AYA cancer survivors were significantly less often employed compared with their controls 1 year (76.1% versus 79.5%, P < 0.001) and 5 years (79.3% versus 83.5%, P < 0.001) after diagnosis, and received more often disability benefits (9.9% versus 3.1% 1 year after diagnosis, P < 0.001; 11.2% versus 3.8% 5 years after diagnosis, P < 0.001). Unemployed AYAs were more often diagnosed with higher disease stages (P < 0.001), treated with chemotherapy (P < 0.001), radiotherapy (P < 0.001) or hormone therapy (P < 0.05) and less often with local surgery (P < 0.05) compared with employed AYAs 1 and 5 years after diagnosis. Based on objective, nationwide, population-based registry data, AYAs' employment and financial outcomes are significantly affected compared with age- and sex-matched controls, both short and long-term after cancer diagnosis. Providing support regarding employment and financial outcomes from diagnosis onwards may help AYAs finding their way (back) into society.

P1170: INCIDENCE, TREATMENT AND OUTCOME OF PATIENTS WITH RICHTER’S SYNDROME: A POPULATION-BASED COHORT STUDY IN THE NETHERLANDS

Background: Richter’s syndrome is a rare aggressive transformation of chronic lymphocytic leukaemia (CLL) into a diffuse large B-cell lymphoma (RS-DLBCL) or Hodgkin lymphoma. Patients with RS-DLBCL have an average overall survival (OS) of 6-12 months. Survival of RS-DLBCL patients previously treated for their CLL is inferior as compared to patients with a previously untreated CLL. In recent years, management of CLL has changed with the introduction of novel agents. Aims: This study evaluates the clinical characteristics, treatment and survival of RS-DLBCL patients in a contemporary era of CLL management in the Netherlands. Methods: DLBCL patients ≥18 years diagnosed in 2014-2020 were identified in the Netherlands Cancer Registry (NCR), with survival follow-up through February 1st, 2021. A prior CLL, diagnosed in 2014-2019, was identified through cross-linkage with the NCR. For these patients, detailed information on CLL and RS-DLBCL treatment was available. Patients with CLL and DLBCL diagnosis within a time interval of 3 months were defined as concurrent RS-DLBCL (concurrent RS). The primary endpoint was overall survival (OS). OS was defined as the time between diagnosis and death from any cause and presented for three subgroups of RS-DLBCL patients, 1) concurrent RS, 2) RS-DLBCL following treated CLL (treated RS), and 3) RS-DLBCL following untreated CLL (untreated RS). Results: A total of 110 patients with RS-DLBCL (median age 72 years, range 43-89 years; 61% males) were selected, including 22 (20%) concurrent RS, 38 (35%) treated RS, and 50 (45%) untreated RS. The majority of patients were diagnosed with stage III/IV RS-DLBCL, i.e., 55% of the concurrent RS were diagnosed with advanced disease as compared to 70% and 79% of the untreated and treated RS, respectively. Median time from CLL to RS diagnosis was for untreated RS 23.2 months (range, 3.4-74.4 months) and for treated RS 17.4 months (range, 4.7-67.5 months). Of the 38 treated RS patients, 30 patients had received rituximab in combination with either chlorambucil (n=11), purine analogues (n=8) or chemotherapeutic regimens such as cyclophosphamide-vincristine-prednisolonie (n=11). Seven patients received treatment including ibrutinib or venetoclax, and 3 patients received treatment not including one or more of the abovementioned regimens. Regarding primary treatment of all RS-DLBCL patients, 19 (86%) out of 22 concurrent RS patients received R-CHO(E)P, 2 patients received another R-based chemotherapy, and 1 patient did not receive therapy. Of the 88 (un)treated RS patients, 59 (67%) received R-CHO(E)P of whom 6 patients were consolidated with autologous stem cell transplantation (SCT) and 2 patients with allogenic SCT. Of the 29 remaining patients, 17 (19%) were treated with a R-based chemotherapy regimen including R-PECC and R-bendamustine, and 12 (14%) patients did not receive therapy. The overall response rate (≥partial remission) of concurrent RS patients was superior as compared to untreated and treated RS patients (86% vs. 70% vs. 55%, respectively; p<0.01). With a median follow-up of 9.5 months (range 0.3-78.3), 3-years OS was 64% for patients with concurrent RS, 53% for untreated RS patients and 5% for treated RS patients (Figure; p<0.01). Image:Summary/Conclusion: In this contemporary population-based study, concurrent RS patients have superior OS, while survival among treated RS patients is very poor. Our data underline the importance of development of new strategies, specifically aiming at treated RS patients.