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Background: Treatment for oesophageal cancer has evolved due to developments including the centralisation of surgery and introduction of neoadjuvant treatment. Therefore, this study evaluated trends in stage distribution, treatment and survival of oesophageal cancer patients in the last 26 years in the Netherlands.Patients and methods: Patients with oesophageal cancer diagnosed in the period 1989-2014 were selected from the Netherlands Cancer Registry. Patients were divided into two groups: non-metastatic (M0) and metastatic (M1). Trends in stage distribution, treatment and relative survival rates were evaluated according to histology.Results: Among all 35,760 patients, the percentage of an unknown tumour stage decreased from 34% to 10% during the study period, whereas the percentage of patients with metastatic disease increased from 21% to 34%. Among surgically treated patients 32% underwent a resection in a high-volume hospital in 2005 which increased to 92% in 2014. Use of neoadjuvant chemoradiotherapy increased in non-metastatic oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) patients from respectively 4% and 2% in 2000-2004 to 43% and 26% in 2010-2014. Five-year relative survival increased from 8% to 22% for all patients; from 12% to 36% for non-metastatic OAC and from 9% to 27% for non-metastatic OSCC over 26 years. Median overall survival of metastatic patients improved from 18 to 22 weeks.Conclusion: In the Netherlands, survival for oesophageal cancer patients improved significantly, especially in the period 2005-2014 which might be the result of better treatment related to the centralisation of surgery and introduction of neoadjuvant chemoradiotherapy. (C) 2018 Elsevier Ltd. All rights reserved.

Background Preliminary data from the TRAP study demonstrated feasibility of neoadjuvant chemoradiation (nCRT) with trastuzumab and pertuzumab. Here, we present updated survival results with propensity score matching, including potential predictive biomarkers for response to this treatment. Methods Patients (pts) with HER2+ resectable esophageal adenocarcinoma (EAC) received nCRT with trastuzumab and pertuzumab (Schokker et al, JCO 2018 suppl. 4057). Survival data was compared with patients not receiving study medication in the Dutch Cancer Registry, using propensity score matching (1:4) based on a logistical regression model, matching for baseline demographic and clinical characteristics. HER2 status was not included as a matching variable, since it was unknown in the majority of pts in the matched cohort. Associations between baseline F-FDG uptake on PET scans, measured by the maximum standardized uptake value (SUVmax), or ΔSUVmax and pathological complete response (pCR) were assessed. Furthermore, expression of HER2 and growth factor receptor-bound protein (Grb)7 was assessed by immunohistochemistry on baseline biopsies. Results were correlated with pCR and survival. Results 40 pts were enrolled and pCR was seen in 34%. Progression-free survival (PFS) rates at 1 and 3 years were 83% and 72%, respectively, with 1- and 3-year overall survival (OS) rates of 90% and 71% (median follow-up 32.1 months). A statistically significant difference in OS was observed for nCRT with trastuzumab and pertuzumab compared to nCRT (3-year OS rate 71% vs 54%, p = 0.039). Baseline and post-treatment PET scans were available for 40 and 34 pts, respectively. Baseline SUVmax was not predictive for recurrence or death, neither did ΔSUVmax correlate with pCR (p > 0.05). HER2 3+ pts and pts with Grb7+ tumours at baseline demonstrated a significantly better response to treatment (p = 0.016 respectively p = 0.007). Conclusions Compared to a propensity score matched cohort receiving nCRT, OS of pts with resectable HER2+ EAC receiving nCRT with trastuzumab and pertuzumab is statistically better. Grb7 and HER2 3+ are potential predictive biomarkers for response to this treatment. Clinical trial identification NCT02120911 April 23, 2014. Legal entity responsible for the study The authors. Funding Roche. Disclosure R.H.A. Verhoeven: Research grant / Funding (self): Roche; Research grant / Funding (self): Bristol-Myers Squibb. M. van Oijen: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Nordic. G.A.P. Hospers: Advisory / Consultancy, Payment to institution: Amgen; Advisory / Consultancy, Payment to institution: Roche; Advisory / Consultancy, Payment to institution: MSD; Advisory / Consultancy, Research grant / Funding (institution), Payment to institution: BMS; Advisory / Consultancy, Payment to institution: Pfizer; Advisory / Consultancy, Payment to institution: Novartis; Research grant / Funding (institution), Payment to institution: Seerave. M. Bijlsma: Research grant / Funding (institution): Celgene; Advisory / Consultancy: Servier. M.I. van Berge Henegouwen: Honoraria (institution), Research grant / Funding (institution): Stryker; Honoraria (institution), Research grant / Funding (institution): Olympus; Honoraria (institution), Advisory / Consultancy: Medtronic; Honoraria (institution), Research grant / Funding (institution): Mylan. H.W.M. van Laarhoven: Honoraria (self), Advisory / Consultancy: Lilly/ImClone; Advisory / Consultancy, Research grant / Funding (institution): Nordic Group; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Bayer Schering Pharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Philips Healthcare; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Merck Sharp & Dohme. All other authors have declared no conflicts of interest.

Background The purpose of the study was to determine the effectiveness of routine follow-up to detect contralateral breast cancer (CBC) in young women. Methods We used the data of the population-based Eindhoven Cancer Registry, which covers the southern part of the Netherlands. Between 1988 and 2005, 1451 women aged ≤40 years were treated for early-stage breast cancer with breast-conserving treatment or mastectomy. Results Of the 94 patients who developed CBC 17 had an in situ carcinoma. Fifty-seven CBCs (61%) were diagnosed more than 5 years after the primary tumour. Forty-two CBCs (45%) were detected during routine follow-up visits, while 52 (55%) presented between two visits. Of the CBC diagnosed between two visits, only 27 (60%) were visible on mammography. Of the invasive CBCs more than 25% was larger than 2 cm in diameter and in 34% positive axillary lymph nodes were found. Conclusions These figures indicate that routine follow-up does not guarantee early detection of CBC in young women with breast cancer.

Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972–2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7–2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6–4.3; AER: 66 patients per 10 000 per year) followed by skin cancer (SIR: 1.7, 95% CI: 1.1–2.6; AER: 17 patients per 10 000 per year). The increased risk of second breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3–2.7) and contralateral (SIR: 2.0, 95% CI: 1.4–2.8) breast. Risk of second cancer was independent of age at diagnosis, type of initial therapy, histologic type of BCIS and period of diagnosis. Standardised incidence ratios of second cancer after BCIS (SIR: 2.3, 95% CI: 1.8–2.8) resembled that after invasive breast cancer (SIR: 2.2, 95% CI: 2.1–2.4). Surveillance should be directed towards second (ipsi- and contra-lateral) breast cancer.

The prevalence of coexistent diseases in addition to breast cancer becomes increasingly important in an ageing population. However, the clinical implications are unclear. The age-specific prevalence of serious comorbidity among all new breast cancer patients diagnosed from 1995 to 2001 (n=8966) in the South of the Netherlands was analysed in relation to age, stage and treatment. Independent prognostic effects of age and comorbidity were evaluated (follow-up was continued until 1 January 2004). The prevalence of comorbidity increased from 9% for those aged

In the present study, we investigated whether age and serious comorbid conditions influence treatment decisions, complications and survival in breast cancer patients. The Eindhoven Cancer Registry records patient, tumour and therapy characteristics of all patients diagnosed with cancer in the southern part of the Netherlands. Additional information on severity of comorbidity and serious complications was collected for a random sample of 527 breast cancer patients (aged 40 years and older). More than 70% of the patients >or=80 exhibited high severity of comorbidity compared to 6% of those aged 40-49 years. Treatment was not influenced by severity of comorbidity. Less than 30% of the breast cancer patients had complications after diagnosis. The number of complications was not related to age or severity of comorbidity. The hazard ratio (HR) of dying for patients with low/moderate severity of comorbidity was 2.4 for those aged 40-69 years and 1.6 for those aged >or=70 years, after adjustment for age, nodal status and treatment. For patients with high severity of comorbidity, the risk of dying was almost three times higher. Older breast cancer patients with serious comorbidity were not treated differently and did not have more complications compared to those without comorbidity, but they exhibited a worse prognosis.

AimTo evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a large, population-based cohort of women aged ⩽40 years with early-stage breast cancer.MethodsAll women (n = 1143) aged ⩽40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast.ResultsAfter a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively (p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (⩽5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407).ConclusionLocal control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.Keywords: Breast carcinoma, Breast-conservation, Local recurrence, Prognosis, Risk, Young age

Background: The use of sentinel node biopsy (SNB), lymph node dissection, breast-conserving surgery, radiotherapy, chemotherapy and hormonal treatment for breast cancer was evaluated in relation to socioeconomic status (SES) in the Netherlands, where access to care was assumed to be equal. Methods: Female breast cancer patients diagnosed between 1994 and 2008 were selected from the nationwide population-based Netherlands Cancer Registry (N=176 505). Socioeconomic status was assessed based on income, employment and education at postal code level. Multivariable models included age, year of diagnosis and stage. Results: Sentinal node biopsy was less often applied in high-SES patients (multivariable analyses, ⩽49 years: odds ratio (OR) 0.70 (95% CI: 0.56–0.89); 50–75 years: 0.85 (0.73–0.99)). Additionally, lymph node dissection was less common in low-SES patients aged ⩾76 years (OR 1.34 (0.95–1.89)). Socioeconomic status-related differences in treatment were only significant in the age group 50–75 years. High-SES women with stage T1–2 were more likely to undergo breast-conserving surgery (+radiotherapy) (OR 1.15 (1.09–1.22) and OR 1.16 (1.09–1.22), respectively). Chemotherapy use among node-positive patients was higher in the high-SES group, but was not significant in multivariable analysis. Hormonal therapy was not related to SES. Conclusion: Small but significant differences were observed in the use of SNB, lymph node dissection and breast-conserving surgery according to SES in Dutch breast cancer patients despite assumed equal access to health care.

Aim To investigate the long-term prognosis of patients with axillary recurrence after axillary dissection for invasive breast cancer and describe the long-term survivors. Methods Between 1984 and 1994, 4669 patients with invasive breast cancer underwent axillary dissection in eight community hospitals in the south–eastern part of The Netherlands. Using follow-up data of the population-based Eindhoven Cancer Registry, 59 patients with axillary recurrence were identified. Results The median interval between treatment of the primary tumour and diagnosis of axillary recurrence was 2.6 years (range 0.3–10.7). The median length of follow-up after diagnosis of axillary recurrence was 11.1 years (5.7–15.6). Distant metastases occurred in 38 of the 59 patients. The 5- and 10-year distant recurrence-free survival rates were 39% (95% CI: 25–52%) and 29% (95% CI: 16–42%). Conclusions Axillary recurrence following axillary dissection is associated with a high rate of subsequent distant metastasis and poor overall prognosis but is not always a fatal event. Our results show that it is possible to cure about one-third of the patients.

Aim: This study was undertaken to gain insight into the risk factors for axillary recurrence among patients with invasive breast cancer who underwent breast-conserving treatment or mastectomy and axillary lymph node dissection. Methods: In a matched case-control design, 59 patients with axillary recurrence and 295 randomly selected control patients without axillary recurrence were compared. Matching factors included age, year of incidence of the primary tumour and postsurgical axillary nodal status. Results: For patients with negative axillary lymph nodes, those with a tumour in the medial part of the breast had a 73% (95% Cl: 4-92%) lower risk of axillary recurrence compared to those with a tumour in the lateral part of the breast. For the patients with positive axillary lymph nodes the risk of axillary recurrence was 65% (95% Cl: 16-86%) lower for those who had received axillary irradiation compared to those without axillary irradiation. Within the age group

Background The aim was to gain insight into the diagnosis, treatment and prognosis of axillary recurrence after axillary clearance for invasive breast cancer in a large patient series. Methods Between 1984 and 1994, 4669 patients with invasive breast cancer underwent axillary clearance in eight community hospitals in the south-eastern part of the Netherlands. Using follow-up data in a population-based cancer registry, 59 patients with axillary recurrence were identified. Results The median interval between treatment of the primary tumour and the diagnosis of axillary recurrence was 2·6 (range 0·3–10·7) years. In 51 patients (86 per cent), axillary recurrence was found by palpation during routine follow-up. Surgery was part of the treatment of recurrence for 41 of 59 patients. Regional control (complete eradication of axillary recurrence) was achieved in 34 patients (58 per cent). The 5-year actuarial survival rate was 39 (95 per cent confidence interval 25–53) per cent. Patients with negative axillary lymph nodes at the time of diagnosis of the primary tumour and complete eradication of axillary recurrence had the best prognosis. Conclusion Patients with axillary recurrence had a poor prognosis, except when complete eradication was achieved and axillary lymph nodes were negative at the time of diagnosis of the primary tumour.