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Data on the age-specific incidence of esophageal cancer are lacking. Our aim was to investigate the age-stratified incidence, treatment, and survival trends of esophageal cancer in the Netherlands, with a focus on adults <50 years. Patients diagnosed with esophageal cancer were included from the nationwide Netherlands Cancer Registry (1989–2018). Follow-up data were available until 31 December 2018. Annual percentage changes of incidence were analyzed according to age group (<50, 50–74, and ≥75 years) and histology type: adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). Treatment trends and relative survival rates (RSR) were estimated by age and stage grouping. A total 59,584 patients were included. In adults <50 years, EAC incidence tripled (mean increase per year: males 1.5%, females 3%), while the incidence of ESCC decreased (mean decrease per year: males −5.3%, females −4.3%). Patients <50 years more often presented with advanced disease stages compared to older patients and were more likely to receive multimodality treatments. Most patients <50 years with potentially curable disease were treated with neoadjuvant chemoradiotherapy followed by surgery compared to patients 50–74 and ≥75 years (74% vs. 55% vs. 15%, respectively; p <.001), and received more frequent systemic therapy once staged with palliative disease (72% vs. 54% vs. 19%, respectively; p <.001). The largest RSR improvement was seen in patients <50 years with early-stage (five years: +47%), potentially curable (five years: +22%), and palliative disease (one year: +11%). Over time, a trend of increasing survival difference was seen between patients <50 and ≥75 years with potentially curable (five-year difference: 17% to 27%) and palliative disease (one-year difference: 11% to 20%). The incidence of EAC is increasing in adults <50 years in the Netherlands. Differences in the use of multimodality treatments with curative or life-prolonging intent in different age categories may account for increasing survival gaps. [ABSTRACT FROM AUTHOR]

In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially. • In 2016 less primary rectal cancer patients were treated with neoadjuvant (chemo)radiotherapy. • The LRRC rate remained the same between 2011 and 2016. • In 2016 LRRC patients were more often candidate for curative treatment. • In 2016 LRRC patients received full course chemoradiotherapy more often. • Survival of curatively treated LRRC patients increased significantly over time. [ABSTRACT FROM AUTHOR]

With increasing interest in organ-preserving strategies for potentially curable esophageal cancer, real-world data is needed to understand the impact of pathological tumor response after neoadjuvant chemoradiotherapy (CRT) on patient outcome. The objective of this study is to assess the association between pathological tumor response following CROSS neoadjuvant CRT and long-term overall survival (OS) in a nationwide cohort. All patients diagnosed in the Netherlands with potentially curable esophageal cancer between 2009 and 2017, and treated with neoadjuvant CRT followed by esophagectomy were included. Through record linkage with the nationwide Dutch Pathology Registry (PALGA), pathological data were obtained. The primary outcome was pathological tumor response based on ypTNM, classified into pathological complete response (ypT0N0) and incomplete responders (ypT0N+, ypT+N0, and ypT+N+). Multivariable logistic and Cox regression models were used to identify predictors of pathological complete response (pCR) and survival. A total of 4946 patients were included. Overall, 24% achieved pCR, with 19% in adenocarcinoma and 42% in squamous cell carcinoma. Patients with pCR had a better estimated 5-year OS compared to incomplete responders (62% vs. 38%, p<.001). Of the patients with incomplete response, ypT+N+ patients (32% of total population) had the lowest estimated 5-year OS rate, followed by ypT0N+ and ypT+ N0 (22%, 47%, and 49%, respectively, p<.001). Adenocarcinoma, well to moderate differentiation, cT3-4, cN+, signet ring cell differentiation and lymph node yield (≥15) were associated with lower likelihood of pCR. In this population-based study, pathological tumor response based on the ypTNM-stage was associated with different prognostic subgroups. A quarter of patients achieved ypT0N0 with favorable long-term survival, while one-third had an ypT+N+ response with very poor survival. The association between pathological tumor response and long-term survival could help in more accurate assessments of individual prognosis and treatment decisions. [ABSTRACT FROM AUTHOR]

Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage III endometrial cancer (EC) have a substantial risk of adverse outcomes. After surgery, adjuvant therapy is recommended with external beam radiotherapy (EBRT), chemotherapy (CT) or both EBRT and CT. Recent trials suggest that EBRT + CT is superior to EBRT or CT alone but also results in more toxicity. We have compared the outcome of different adjuvant treatments in a population-based cohort to identify subgroups that benefit most from EBRT + CT. All patients diagnosed with FIGO stage III EC and treated with surgery in 2005–2016 were identified from the Netherlands Cancer Registry. The primary outcome was overall survival (OS); associations with adjuvant treatment were analysed using Cox regression analysis. Among 1241 eligible patients, EBRT + CT was associated with a better OS than CT (hazard ratio [HR] = 1.84, 95% confidence interval [CI] = 1.34–2.52) and EBRT alone (HR = 1.37, 95% CI = 1.05–1.79). In stage IIIC, there was a significant benefit of EBRT + CT compared with CT or EBRT alone. In stage IIIA–B, there was no difference between EBRT + CT or EBRT alone. In endometrioid EC (EEC) and carcinosarcomas, EBRT + CT was associated with a better OS than CT or EBRT alone. For uterine serous cancers, there was no survival benefit of EBRT + CT over CT. In all analysis by stage and histology, any adjuvant treatment was superior to no adjuvant therapy. In this population-based study, adjuvant EBRT + CT was associated with improved OS compared with CT or EBRT alone in FIGO stage IIIC EC, EEC and carcinosarcoma. This suggests that application of EBRT + CT in stage III should be further stratified according to these subgroups. • This population-based study investigated adjuvant therapy in stage III endometrial cancer. • Survival after external beam radiotherapy (EBRT) and chemotherapy (CT) was superior to that after CT and radiotherapy alone. • Patients with stage IIIC endometrioid tumours or carcinosarcomas benefited most from EBRT + CT. • EBRT + CT was not superior to CT or radiotherapy alone in stage IIIA/B or serous tumours. [ABSTRACT FROM AUTHOR]

Introduction: Concurrent chemoradiotherapy remains the main treatment strategy for patients with stage IIIA non-small cell lung cancer (NSCLC); stage cT3N1 or cT4N0-1 may be eligible for surgery and potentially resectable stage IIIA (N2) NSCLC for neoadjuvant therapy followed by resection. We evaluated treatment patterns and outcomes of patients with stage IIIA NSCLC in The Netherlands. Material and Methods: Primary treatment data of patients with clinically staged IIIA NSCLC between 2010 and 2016 were extracted from The Netherlands Cancer Registry. Patient characteristics were tabulated and 5-year overall survival (OS) was calculated and reported. Results: In total, 9,591 patients were diagnosed with stage IIIA NSCLC. Of these patients, 41.3% were treated with chemoradiotherapy, 11.6% by upfront surgery and 428 patients (4.5%) received neoadjuvant treatment followed by resection. The 5-year OS was 26% after chemoradiotherapy, 40% after upfront surgery and 54% after neoadjuvant treatment followed by resection. Clinical over staging was seen in 42.3% of the patients that were operated without neoadjuvant therapy. Conclusion: In The Netherlands, between 2010 and 2016, 4.5% of patients with stage IIIA NSCLC were selected for treatment with neoadjuvant therapy followed by resection. The 5-year OS in these patients exceeded 50%. However, the outcome might be overestimated due to clinical over staging. [ABSTRACT FROM AUTHOR]

Accurate, consistent and reproducible grading by pathologists is of key‐importance for identification of individual patients with invasive breast cancer (IBC) that will or will not benefit from adjuvant systemic treatment. We studied the laboratory‐specific grading variation using nationwide real‐life data to create insight and awareness in grading variation. Synoptic pathology reports of all IBC resection‐specimens, obtained between 2013 and 2016, were retrieved from the nationwide Dutch Pathology Registry (PALGA). Absolute differences in laboratory‐proportions of Grades I–III were compared to the national reference. Multivariable logistic regression provided laboratory‐specific odds ratios (ORs) for high‐ vs. low‐grade IBC. 33,792 IBC pathology reports of 33,043 patients from 39 laboratories were included, of which 28.1% were reported as Grade I (range between laboratories 16.3–43.3%), 47.6% as Grade II (38.4–57.8%), and 24.3% as Grade III (15.5–34.3%). Based on national guidelines, the indication for adjuvant chemotherapy was dependent on histologic grade in 29.9% of patients. After case‐mix correction, 20 laboratories (51.3%) showed a significantly deviant OR. Significant grading differences were also observed among pathologists within laboratories. In this cohort of 33,043 breast cancer patients, we observed substantial inter‐ and intra‐laboratory variation in histologic grading. It can be anticipated that this has influenced outcome including exposure to unnecessary toxicity, since choice of adjuvant chemotherapy was dependent on grade in nearly a third of patients. Better standardization and training seems warranted. What's new? Histologic grade serves a critical prognostic role in invasive breast cancer (IBC) and is used to guide therapeutic decisions. Evidence indicates, however, that IBC grading varies considerably. Here, grading variation in clinical practice was evaluated using real‐life data from laboratories in the nationwide Dutch Pathology Registry. Laboratories varied in IBC grade I, II, and III reporting. Among grading components, nuclear polymorphism showed the greatest difference between laboratories. Within laboratories, one‐third of pathologists deviated significantly from national proportions for IBC grade I. Despite deployment of uniform guidelines across laboratories, IBC histologic grading is not necessarily performed in a consistent manner. [ABSTRACT FROM AUTHOR]

Accurate clinical staging of rectal cancer is hampered by suboptimal sensitivity of MRI in the detection of regional lymph node metastases. Consequently, some patients may be understaged and have been withheld neoadjuvant (chemo)radiotherapy in retrospect. Although Dutch guidelines do not advocate adjuvant chemotherapy (ACT) in rectal cancer, some of these clinically understaged patients receive ACT according to local policy. We aim to assess the benefit of ACT in these patients. Population-based data from patients with clinically node-negative (cN0) but pathologically node-positive (pN+) rectal cancer that underwent total mesorectal excision (TME) without neoadjuvant treatment between 2008 and 2018 were obtained from the Netherlands Cancer Registry. Missing data were handled by multiple imputation. Stabilised inverse probability treatment weighting (sIPTW) was used to balance clinical characteristics. Overall survival (OS) was compared in ACT and non-ACT patients. Of 34,724 patients, 13,861 had cN0 disease of whom 3016 were pN+ (21.8%). 1466 (48.6%) of these patients underwent upfront TME and were included. Median follow-up was 84 months (95% confidence interval [CI] 76–97) versus 79 months (95% CI 77–81) in patients that did (n = 290, 19.8%) and did not (n = 1176, 80.2%) receive ACT, respectively. After sIPTW adjustment, ACT was associated with improved OS (hazard ratio 0.70; 95% CI 0.49–0.99; p = 0.04). The estimated 5-year OS rate was 74.2% versus 65.3%, respectively. In this population-based cohort of patients with cN0 but pN+ rectal cancer who underwent upfront TME, ACT was associated with a significant OS benefit. These data support to discuss ACT in this population. • Netherlands Cancer Registry data were collected from 13,861 cN0 rectal cancer patients. • 22% of these patients proved pathologically N+. • 49% of understaged pN+ patients did not receive neoadjuvant (chemo)radiotherapy. • Adjuvant chemotherapy in these understaged pN+ patients improved overall survival. • A consistent survival benefit was observed across subgroups. [ABSTRACT FROM AUTHOR]

Background: Initiation of adjuvant chemotherapy within 6–12 weeks after mastectomy is recommended by guidelines. The aim of this population‐based study was to investigate whether immediate breast reconstruction (IBR) after mastectomy reduces the likelihood of timely initiation of adjuvant chemotherapy. Methods: All patients with breast cancer who had undergone mastectomy and adjuvant chemotherapy between 2012 and 2016 in the Netherlands were identified. Time from surgery to adjuvant chemotherapy was categorized as within 6 weeks or after more than 6 weeks, within 9 weeks or after more than 9 weeks, and within 12 weeks or after more than 12 weeks. The impact of IBR on the initiation of adjuvant chemotherapy for these three scenarios was estimated using propensity score matching to adjust for treatment by indication bias. Results: A total of 6300 patients had undergone primary mastectomy and adjuvant chemotherapy, of whom 1700 (27·0 per cent) had received IBR. Multivariable analysis revealed that IBR reduced the likelihood of receiving adjuvant chemotherapy within 6 weeks (odds ratio (OR) 0·76, 95 per cent c.i. 0·66 to 0·87) and 9 weeks (0·69, 0·54 to 0·87), but not within 12 weeks (OR 0·75, 0·48 to 1·17). Following propensity score matching, IBR only reduced the likelihood of receiving adjuvant chemotherapy within 6 weeks (OR 0·95, 0·90 to 0·99), but not within 9 weeks (OR 0·97, 0·95 to 1·00) or 12 weeks (OR 1·00, 0·99 to 1·01). Conclusion: Postmastectomy IBR marginally reduced the likelihood of receiving adjuvant chemotherapy within 6 weeks, but not within 9 or 12 weeks. Thus, IBR is not contraindicated in patients who need adjuvant chemotherapy after mastectomy. [ABSTRACT FROM AUTHOR]

The benefit of adjuvant chemotherapy for FIGO stage I, high-grade serous ovarian cancer (HGSOC) after optimal staging is a matter of debate. We investigated the effect of adjuvant chemotherapy on recurrence-free survival (RFS) and overall survival (OS) in a population-based cohort study. All patients diagnosed in the Netherlands between 2002 and 2014 with FIGO stage I HGSOC who underwent surgical staging were included. Data on clinical characteristics, histopathology, completeness of staging and survival were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. Recurrence data was collected from hospital files. We used Kaplan-Meier methods to estimate RFS and OS and Cox-proportional hazard analyses to control for differences in baseline characteristics between patients who did or did not receive chemotherapy. We identified 223 patients who underwent optimal staging procedures including lymph node sampling. Events of disease recurrence occurred in 21 of the 101 patients (21%) who received adjuvant chemotherapy and in 46 of the 122 patients (38%) who did not (multivariable hazard ratio (HR), 0.37; 95%CI 0.22–0.64; p < 0.01). Five-year RFS was 81% after staging plus chemotherapy and 59% after staging only. At a median follow-up of 105 months, 21 patients (21%) in the chemotherapy group and 38 patients (31%) in the no-chemotherapy group had died (multivariable HR 0.50; 95%CI 0.28–0.89; p = 0.02). Ten-year OS was 78% with chemotherapy and 62% without chemotherapy. Adjuvant chemotherapy improves long-term RFS and OS in patients with FIGO stage I HGSOC after optimal staging. • Until now, no consensus has been reached on the benefit of adjuvant chemotherapy for early stage HGSOC. • After optimal staging and FIGO stage I HGSOC, adjuvant chemotherapy favors long-term RFS and OS. • Chemotherapy should be considered after optimal staging for FIGO stage I HGSOC to improve RFS and OS. [ABSTRACT FROM AUTHOR]

Background: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM.Methods: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone.Discussion: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival.Trial Registration: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018. [ABSTRACT FROM AUTHOR]

Objective: Uterine carcinosarcoma is a rare, aggressive subtype of endometrial cancer. Treatment consists of hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy (LND). The survival benefit of LND in relation to adjuvant radio- and/or chemotherapy is unclear. We evaluated the impact of LND on survival in relation to adjuvant therapy in uterine carcinosarcoma. Methods: Retrospective data on 1,140 cases were combined from the Netherlands Cancer Registry (NCR) and the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). LND was defined as the removal of any nodes. Additionally, cases where 10 nodes or less (LND ≤10) or more than 10 nodes (LND > 10) were removed were analyzed separately. Adjuvant therapy was evaluated as radiotherapy, chemotherapy, or radiochemotherapy. Associations were analyzed by χ2 test, log-rank test, and Cox regression analysis. Results: Overall survival (OS) had improved after total abdominal hysterectomy with bilateral salpingo-oophorectomy with LND > 10 (HR 0.62, 95% CI 0.47–0.83). Adjuvant therapy was related to OS with an HR of 0.64 (95% CI 0.54–0.75) for radiotherapy, an HR of 0.65 (95% CI 0.48–0.88) for chemotherapy, and an HR of 0.25 (95% CI 0.13–0.46) for radiochemotherapy. Additionally, adjuvant treatment was related to OS when lymph nodes were positive (HR 0.22, 95% CI 0.11–0.42), but not when they were negative. Conclusion: LND is related to improved survival when more than 10 nodes are removed. Adjuvant therapy improves survival when LND is omitted, or when nodes are positive. [ABSTRACT FROM AUTHOR]

Background: The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen.Methods: DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands. We randomly assigned postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2-3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans European Network for Clinical Trials Services) for the randomisation procedure. Stratification factors were nodal status, hormone receptor status, HER2 status, and tamoxifen treatment duration. The primary study endpoint of this analysis was disease-free survival starting beyond 3 years after randomisation (adapted disease-free survival). Here we report the final analysis from the DATA trial, which is registered with ClinicalTrials.gov, number NCT00301457.Findings: Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955 were assigned to the 3-year group and 957 to the 6-year anastrozole treatment group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year group) and 1660 were disease free 3 years after randomisation. The 5-year adapted disease-free survival was 83·1% (95% CI 80·0-86·3) in the 6-year group and 79·4% (76·1-82·8) in the 3-year group (hazard ratio [HR] 0·79 [95% CI 0·62-1·02]; p=0·066). Patients in the 6-year treatment group had more adverse events than those in the 3-year treatment group, including all-grade arthralgia or myalgia (478 [58%] of 827 in the 6-year treatment group vs 438 [53%] of 833 in the 3-year treatment group) and osteopenia or osteoporosis (173 [21%] vs 137 [16%]).Interpretation: We cannot recommend the use of extended adjuvant aromatase inhibition after 5 years of sequential endocrine therapy in all postmenopausal women with hormone receptor-positive breast cancer.Funding: AstraZeneca. [ABSTRACT FROM AUTHOR]

Background: We aimed to assess whether socioeconomic status (SES) and ethnicity affect adjuvant systemic therapy (AST) guideline adherence in early breast cancer patients in a health care setting with assumed equal access to care. Methods: Data from all female patients surgically treated for primary unifocal early breast cancer between January 2005 and December 2014 were retrieved from the Netherlands Cancer Registry. We assessed the association between SES, ethnicity and non-adherence to adjuvant chemotherapy (CT) or endocrine therapy (ET) guideline indications with Poisson regression models, adjusting for clinicopathological variables. Results: A total of 104 201 patients were included in the current analysis. Of patients without an indication, 4% and 13% received adjuvant CT or ET (overtreatment), whereas 39% and 14% of patients with an indication did not receive CT or ET (undertreatment). Medium and low SES patients were 1.01 (95% CI 1.00-1.01) and 1.01 (95% CI 1.00-1.01) times more likely to be undertreated and 0.85 (95% CI 0.76-0.94) and 0.67 (95% CI 0.60-0.75) times more likely to be overtreated with CT compared with high SES patients [resulting in an overall relative risk of CT use of 0.94 (95% CI 0.92-0.96) and 0.85 (95% CI 0.83-0.87), respectively]. No association between SES and ET guideline adherence or ethnicity and CT/ET guideline adherence was observed. Conclusion: In the Netherlands, minimal SES disparities in CT guideline adherence were observed: low SES patients are less likely be overtreated and marginally more likely to be undertreated with CT resulting in an overall decreased risk of receiving CT. No ethnical disparities in AST guideline adherence were observed. [ABSTRACT FROM AUTHOR]

Background: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. Methods: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Results: Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Conclusions: Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. [ABSTRACT FROM AUTHOR]

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers ( UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Treatment variation is an important issue in health care provision. An external peer review programme for multidisciplinary cancer care was introduced in 1994 in the Netherlands to improve the multidisciplinary organisation of cancer care in hospitals. So far the clinical impact of external quality assessment programmes such as external peer review and accreditation remains unclear. Our objective was to examine the degree of variation in treatment patterns and the possible effect of external peer review for multidisciplinary cancer care for breast cancer patients. Methods: Patients with breast cancer were included from 23 hospitals from two 'intervention regions' with the longest experience with the programme and 7 hospitals that never participated (control group). Data on tumour and treatment characteristics were retrieved from the Netherlands Cancer Registry. Treatment modalities investigated were: the completeness of breast conserving therapy, introduction of the sentinel node biopsy, radiotherapy after breast conserving surgery for ductal carcinoma in situ (DCIS), adjuvant radiotherapy for locally advanced breast cancer (T3/M0 or any T,N2-3/M0), adjuvant chemotherapy for early stage breast cancer (T1-2/N+/M0) and neo-adjuvant chemotherapy for T4/M0 breast cancer. Hospitals from the two intervention regions were dichotomised based on their implementation proportion (IP) of recommendations from the final reports of each peer review (high IP vs. low IP). This was regarded as a measure of how well a hospital participated in the programme. Results: 63,516 female breast cancer patients were included (1990-2010). Variation in treatment patterns was observed between the intervention regions and control group. Multidisciplinary treatment patterns were not consistently better for patients from hospitals with a high IP. Conclusions: There is no relationship between the external peer review programme for multidisciplinary cancer care and multidisciplinary treatment patterns for breast cancer patients. Regional factors seem to exert a stronger effect on treatment patterns than hospital participation in external peer review. [ABSTRACT FROM AUTHOR]

Background We evaluated which patient factors were associated with treatment tolerance and outcome in elderly colon cancer patients. Design Population-based data from five regions included in the Netherlands Cancer Registry were used. Patients with resected stage III colon cancer aged ≥75 years diagnosed in 1997–2004 who received adjuvant chemotherapy (N = 216) were included as well as a random sample (N = 341) of patients who only underwent surgery. Results The most common motives for withholding adjuvant chemotherapy were a combination of high age, co-morbidity and poor performance status (PS, 43%) or refusal by the patient or family (17%). In 57% of patients receiving chemotherapy, adaptations were made in treatment regimens. Patients who received adjuvant chemotherapy developed more complications (52%) than those with surgery alone (41%). For the selection of patients who had survived the first year after surgery, receiving adjuvant chemotherapy resulted in better 5-year overall survival (52% versus 34%), even after adjustment for differences in age, co-morbidity and PS. Conclusion Despite high toxicity rates and adjustments in treatment regimens, elderly patients who received chemotherapy seemed to have a better survival. Prospective studies are needed for evaluating which patient characteristics predict the risks and benefits of adjuvant chemotherapy in elderly colon cancer patients. [ABSTRACT FROM PUBLISHER]

Background We determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival. Patients and methods Data from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997–2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed. Results The proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997–2000 to 23% in 2007–2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997–2000 to 35% in 2004–2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4–0.5). Conclusion There has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment. [ABSTRACT FROM AUTHOR]

Association of Surgeons from the Netherlands (ASN), Springmeeting ('Chirurgendagen'), 10 & 11 May 2012, Veldhoven, the Netherlands Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In the past decades, much attention has been given to the risks of undertreatment of cancer in older patients. We set out to determine whether current treatment of colon cancer in older patients still differs from younger patients and to identify risk factors and physician''s reasons for deviation from Dutch treatment guidelines. Patients and methods: Retrospective cohort study of all consecutive patients newly diagnosed with colon cancer at the Slotervaart Hospital in Amsterdam from January 2002 to December 2007. Data were collected using clinical charts. Results: Of 286 patients, 183 were 70years or older. Ninety-one percent of older patients received curative surgery and 32% received adjuvant chemotherapy in accordance with guidelines compared to 100% and 85% in the younger group (p=0.002 and p<0.001 respectively). The primary reasons stated by the treating physician for withholding surgery were comorbidity and poor general health. For adjuvant chemotherapy, the main reason stated was age. For both surgery and chemotherapy, multivariate analysis revealed that deviation from guidelines was most strongly associated with age (surgery OR 1.18 (CI 1.06–1.30); p=0.002 and chemotherapy OR 1.19 (CI 1.08–1.31); p<0.001 respectively). Despite this selection, older patients experienced more postoperative morbidity and mortality than younger patients. Chemotherapy toxicity was equal in both groups, despite less aggressive regimens for older patients. Conclusion: At our centre, guideline adherence for surgery in older patients was high, and deviations were well motivated. Age still seems to be the most important factor for withholding chemotherapy, despite evidence suggesting benefit in selected older patients. [Copyright &y& Elsevier]

Background: We described changes in treatment of colon cancer over time and the impact on survival in The Netherlands in the period 1989–2006.Patients and methods: All 103 744 patients with invasive colon cancer during 1989–2006 in The Netherlands were included. Data were extracted from The Netherlands Cancer Registry. Trends in treatment over time were analysed and multivariable relative survival analysis was carried out.Results: The administration of adjuvant chemotherapy in stage III patients <75 years increased from 19% in 1989–1993 to 79% in 2004–2006 and from 1% to 19% in stage III patients ≥75 years. Among stage IV patients, resection rates of the primary tumour decreased from 72% to 63%, while chemotherapy administration increased from 23% to 64% in those <75 years. Survival increased from 52% to 58% in males and from 55% to 58% among females. Stage III patients with adjuvant chemotherapy exhibited a relative excess risk of 0.4 (95% confidence interval 0.4–0.4) compared with those without. Among stage IV patients, resection of primary tumour, palliative chemotherapy, and metastasectomy were important prognostic factors.Conclusions: There were substantial improvements in management and survival of colon cancer from 1989 to 2006. Stage III disease patients with colon cancer experienced the largest improvement in survival, most likely related to the increased administration of adjuvant chemotherapy. [ABSTRACT FROM PUBLISHER]

Background: The association of isolated tumor cells and micrometastases in regional lymph nodes with the clinical outcome of breast cancer is unclear. Methods: We identified all patients in the Netherlands who underwent a sentinel-node biopsy for breast cancer before 2006 and had breast cancer with favorable primary-tumor characteristics and isolated tumor cells or micrometastases in the regional lymph nodes. Patients with node-negative disease were randomly selected from the years 2000 and 2001. The primary end point was disease-free survival. Results: We identified 856 patients with node-negative disease who had not received systemic adjuvant therapy (the node-negative, no-adjuvant-therapy cohort), 856 patients with isolated tumor cells or micrometastases who had not received systemic adjuvant therapy (the node-positive, no-adjuvant-therapy cohort), and 995 patients with isolated tumor cells or micrometastases who had received such treatment (the node-positive, adjuvant-therapy cohort). The median follow-up was 5.1 years. The adjusted hazard ratio for disease events among patients with isolated tumor cells who did not receive systemic therapy, as compared with women with node-negative disease, was 1.50 (95% confidence interval [CI], 1.15 to 1.94); among patients with micrometastases, the adjusted hazard ratio was 1.56 (95% CI, 1.15 to 2.13). Among patients with isolated tumor cells or micrometastases, the adjusted hazard ratio was 0.57 (95% CI, 0.45 to 0.73) in the node-positive, adjuvant-therapy cohort, as compared with the node-positive, no-adjuvant-therapy cohort. Conclusions: Isolated tumor cells or micrometastases in regional lymph nodes were associated with a reduced 5-year rate of disease-free survival among women with favorable early-stage breast cancer who did not receive adjuvant therapy. In patients with isolated tumor cells or micrometastases who received adjuvant therapy, disease-free survival was improved. N Engl J Med 2009;361:653-63. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate the association between systemic treatments and post-diagnosis weight gain in breast cancer patients during longer follow-up periods, we conducted a retrospective cohort study (n =271). Information on adjuvant systemic treatments and repeated body weight measurements was obtained from medical records, and analysed using multi-level regressions. During the first year, a mean weight change of +2.0kg (SD 4.9) was observed. Overall, 29% of all breast cancer patients had gained 5kg or more in body weight during total follow-up (median: 3 years). In multi-level analyses, women who received combined systemic treatment gained significantly more weight as compared with women who received no systemic treatment (4.5kg versus 2.0kg at 5 years post-diagnosis, p <0.05). Significant weight gain occurs in breast cancer patients in the Netherlands during the first year post-diagnosis. After the first year, further weight gain mainly occurs in women who receive chemotherapy in combination with endocrine therapy. [Copyright &y& Elsevier]

Abstract: Background: This study evaluated trends in adjuvant systemic treatment among breast cancer patients and analyzed the factors on which treatment choice was based. Patients and methods: Patients diagnosed with early stage breast cancer in 1990–2006 were selected from the registry of the Comprehensive Cancer Centre South (n =8261). The probability of receiving therapy was determined per characteristic for the periods 1990–1997, 1998–2001 and 2002–2006, separately. Results: The use of any adjuvant systemic treatment increased from 37% in 1990–1997 to 51% in 1998–2001 and 53% in 2002–2006 (p for trend < 0.0001). In the period 1990–1997, lymph node status (positive vs. negative: probability ratio (PR=25.8; 95% CI, 16.5–40.4) and age (⩾ 60 vs. ⩽ 35 years: PR=0.01; 95% CI, 0.00–0.02) were the main determinants of the likelihood of receiving chemotherapy. From 1998 onwards, age remained the most important factor in decreasing the likelihood of receiving chemotherapy. During 1990–1997 the use of hormonal therapy was mainly determined by positive lymph node status (PR=35; 95% CI, 25–49) and age (⩾ 70 vs. ⩽ 35 years: PR=9.3; 95% CI, 4.4–20), whereas positive hormone receptor status mainly affected hormonal therapy use (PR=17; 95% CI, 10–28) in the period 2002–2006. Marked differences were observed between hospitals in the adoption of adjuvant systemic treatment for node–negative patients. Conclusions: The impact of patient and tumour characteristics on treatment choice varied over time, reflecting major changes in the Dutch treatment guidelines. Patients older than 70 years received almost no chemotherapy. [Copyright &y& Elsevier]

Comments on the use of high-dose chemotherapy (HDC) in high-risk breast cancer. Brief discussion of a report by Sjoerd Rodenhuis et al from the Netherlands Cancer Institute, which is in this issue of `Lancet'; Recommendation that HDC as adjuvant therapy for high-risk breast cancer should not be used in routine clinical practice.

Abstract: Background: Aim of this study was to describe treatment patterns and outcome according to region, and according to hospital types and volumes among patients with colon cancer in the Netherlands. Methods: All patients with invasive colon carcinoma diagnosed in the period 2001–2006 were selected from the Netherlands Cancer Registry. Logistic regression analyses were performed to examine the influence of relevant factors on the odds of having adequate lymph node evaluation, receiving adjuvant chemotherapy and postoperative mortality. Relative survival analysis was used to estimate relative excess risk of dying according to hospital type and volume. Results: In total, 39 907 patients were selected. Patients diagnosed in a university hospital had a higher odds (OR 2.47; 95% CI 2.19–2.78) and patients diagnosed in a hospital with >100 colon carcinoma diagnoses annually had a lower odds (OR 0.70; 95% CI 0.64–0.77) of having ≥10 lymph nodes evaluated. The odds of receiving adjuvant chemotherapy was lower in patients diagnosed in teaching hospitals (OR 0.85; 95% CI 0.73–0.98) and university hospitals (OR 0.56; 95% CI 0.45–0.70) compared to patients diagnosed in non-teaching hospitals. Funnel plots showed large variation in these two outcome measures between individual hospitals. No differences in postoperative mortality were found between hospital types or volumes. Patients diagnosed in university hospitals and patients diagnosed in hospitals with >50 diagnoses of colon carcinoma per year had a better survival. Conclusions: Variation in treatment and outcome of patients with colon cancer in the Netherlands was revealed, with differences between hospital types and volumes. However, variation seemed mainly based on the level of the individual hospital. [ABSTRACT FROM AUTHOR]

Abstract: Background: To describe variation in staging and primary treatment by hospital characteristics including type and volume and region in patients with early breast cancer (BC) in the Netherlands, 2003–2006 after completion of national guidelines in 2002. Methods: All patients newly diagnosed with invasive BC in 2003–2006 and recorded in the Netherlands Cancer Registry were included (n = 51 354). Multivariable logistic regression analyses examined the influence of patient and hospital characteristics, also by region, on type of breast surgery, axillary lymph node dissection (ALND), sentinel node procedure (SNP), and adjuvant irradiation and/or systemic treatment. Results: Patients <40 years more often underwent breast conserving surgery (BCS) in general hospitals (OR 1.4 (95%CI 1.1–1.5)) than in teaching and academic hospitals, whereas patients of 40–69 years less often received BCS in an academic hospital (OR 0.9 (95%CI 0.8–1.0)) than in teaching hospitals. Patients with pT1-2N0 cancer more often underwent primary ALND in a general hospital than in a larger teaching or academic hospital. Type of hospital did not seem to affect utilization of adjuvant systemic therapy, but patient age and tumour size and grade did. Over time, patients more often received SNP, BCS, and adjuvant systemic therapy, primary ALND being on the decline, but with substantial regional variation between geographic regions. Conclusion: With detailed evidence-based national guidelines since 2002 the considerable regional and hospital variation in staging procedures and primary treatment among newly diagnosed patients with early breast cancer in the Netherlands decreased markedly, suggesting the presence of late adaptors rather than specific hospital characteristics. [ABSTRACT FROM AUTHOR]