Support needs of Dutch young adult childhood cancer survivors.

BACKGROUND: Studies about support needs of young adult childhood cancer survivors (YACCS) previously focused mainly on information needs. This study assessed support needs and associated factors (sociodemographic, medical, and psychosocial functioning) in Dutch YACCS. METHODS: YACCS (aged 18-30, diagnosed ≤ 18 years, time since diagnosis ≥ 5 years) cross-sectionally filled out a questionnaire regarding their need for various types of support (concrete information, personal counseling, and peer contact) in eight domains (physical consequences of childhood cancer, social-emotional consequences, relationships and sexuality, fertility, lifestyle, school and work, future perspective, insurance and mortgage), and questionnaires assessing health-related quality of life (PedsQL-YA), anxiety and depression (HADS), and fatigue (CIS-20R). Descriptive statistics were used to describe support needs. Linear regression was used to identify characteristics associated with support needs. RESULTS: One hundred fifty-one YACCS participated (response = 40%). Most YACCS reported a need for support in one or more domains (88.0%, N = 133). More than half of the participants reported a need for concrete information in the domains lifestyle, fertility, and physical consequences of childhood cancer and 25-50% in the domains insurance and mortgages, future perspective, and social-emotional consequences of childhood cancer. In the domains lifestyle and physical as well as emotional consequences of childhood cancer, 25-50% reported a need for counseling. Overall need for support was positively associated with middle (ß = 0.26, p = 0.024) and high (ß = 0.35, p = 0.014) compared to low educational attainment and (sub)clinical anxiety (ß = 0.22, p = 0.017), and negatively associated with social functioning (ß = - 0.37, p = 0.002) in multivariate analyses. CONCLUSION: YACCS report the strongest need for support, for concrete information, in the domains lifestyle, fertility, and physical consequences of childhood cancer. Associated factors were mostly socioeconomic and psychosocial in nature. Psychosocial care should be an integral part of survivorship care for YACCS, with screening for psychosocial problems, information provision including associated emotional consequences and support if necessary (psycho-education) and tailored interventions, and adequate referrals to more specialized care if necessary.

A vulnerable age group: the impact of cancer on the psychosocial well-being of young adult childhood cancer survivors.

PURPOSE: This study aimed to increase our understanding of the psychosocial well-being of young adult childhood cancer survivors (YACCS) as well as the positive and negative impacts of cancer. METHODS: YACCS (aged 18-30, diagnosed ≤ 18, time since diagnosis ≥ 5 years) cross-sectionally filled out the "Pediatric Quality of Life Inventory Young Adults" (PedsQL-YA), "Hospital Anxiety and Depression Scale" (HADS), and "Checklist Individual Strengths" (CIS-20R) to measure fatigue and survivor-specific "Impact of Cancer - Childhood Survivors" (IOC-CS), which measures the long-term impact of childhood cancer in several domains. Descriptive statistics (IOC-CS), logistic regression (HADS, CIS-20R), and ANOVA (PedsQL-YA, HADS, CIS-20R) were performed. Associations between positive and negative impacts of childhood cancer and psychosocial outcomes were examined with linear regression analyses. RESULTS: YACCS (N = 151, 61.6% female, mean age 24.1 ± 3.6, mean time since diagnosis 13.6 ± 3.8) reported lower HRQOL (- .4 ≤ d ≤ - .5, p ≤ .001) and more anxiety (d = .4, p ≤ .001), depression (d = .4, p ≤ .01), and fatigue (.3 ≤ d ≤ .5, p ≤ .001) than young adults from the general Dutch population. They were at an increased risk of experiencing (sub)clinical anxiety (OR = 1.8, p = .017). YACCS reported more impact on scales representing a positive rather than negative impact of CC. Various domains of impact of childhood cancer were related to psychosocial outcomes, especially "Life Challenges" (HRQOL ß = - .18, anxiety ß = .36, depression ß = .29) and "Body & Health" (HRQOL ß = .27, anxiety ß = - .25, depression ß = - .26, fatigue ß = - .47). CONCLUSION: YACCS are vulnerable to psychosocial difficulties, but they also experience positive long-term impacts of childhood cancer. Positive and negative impacts of childhood cancer were associated with psychosocial outcomes in YACCS. Screening of psychosocial outcomes and offering targeted interventions are necessary to optimize psychosocial long-term follow-up care for YACCS.

Long-term effects of childhood cancer treatment on hormonal and ultrasound markers of ovarian reserve.

STUDY QUESTION: Which treatment-related factors are (dose-dependently) associated with abnormal hormonal and ultrasound markers of ovarian reserve in female childhood cancer survivors (CCSs)? SUMMARY ANSWER: Cyclophosphamide, procarbazine, a composite group of 'other alkylating agents', dactinomycin, doxorubicin, mitoxantrone, spinal radiotherapy (RT), abdominal/pelvic RT and total body irradiation were multivariably associated with abnormal ovarian reserve markers, with dose-effect relationships being established for procarbazine and abdominal/pelvic RT. WHAT IS KNOWN ALREADY: Female childhood cancer survivors are at an increased risk of reduced ovarian function and reserve, but knowledge regarding the long-term effects of individual chemotherapeutic (CT) agents and radiotherapy fields and their respective doses is limited. STUDY DESIGN, SIZE, DURATION: The DCOG LATER-VEVO is a nationwide retrospective cohort study in which measurements were performed between 2008 and 2014. In total, 1749 female 5-year CCSs, diagnosed before age 18 years between 1963 and 2002 and 1201 controls were invited for the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian reserve was assessed by anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B levels, and antral follicle counts (AFC). The study was a multicentre study including all seven Dutch Centers for Paediatric Oncology/Haematology. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 564 CCs and 390 controls participated in the clinical part of the study. Overall, 7.0-17.7% of CCSs and 2.4-13.6% of controls had abnormal ovarian reserve markers. Above age 35, significantly more CCSs than controls had abnormal ovarian reserve markers (AMH: 26% vs. 4%; AFC: 20% vs. 3%; inhibin B: 42% vs. 16%). For AMH and FSH, significant differences were also found below age 35. Cyclophosphamide, procarbazine, a group of 'other alkylating agents', dactinomycin, doxorubicin, mitoxantrone, spinal RT, abdominal/pelvic RT and total body irradiation were multivariably associated with at least one abnormal ovarian reserve marker. Dose-effect relationships were established for procarbazine and abdominal/pelvic RT. LIMITATIONS, REASONS FOR CAUTION: Despite the large scale of the study, dose-effect relationships could not be investigated for all types of treatment due to a limited numbers of participants for specific analyses. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrated that the majority of CCSs do not show signs of a reduced ovarian reserve. However, specific subgroups of CCSs appear to be associated with a high risk. Our results are important for counselling CCSs and future patients regarding parenthood and fertility preservation. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20). Philips Health Systems Benelux supported this study by providing three ultrasound systems and concomitant analytic software. There are no competing interests. TRIAL REGISTRATION NUMBER: NTR2922 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 2922.

Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study.

PURPOSE: The Dutch national guideline advises use of gene-expression signatures, such as the 70-gene signature (70-GS), in case of ambivalence regarding the benefit of adjuvant chemotherapy (CT). In this nationwide study, the impact of 70-GS use on the administration of CT in early breast cancer patients with a dubious indication for CT is assessed. METHODS: Patients within a national guideline directed indication area for 70-GS use who were surgically treated between November 2011 and April 2013 were selected from the Netherlands Cancer Registry database. The effect of 70-GS use on the administration of CT was evaluated in guideline- and age-delineated subgroups addressing potential effect of bias by linear mixed-effect modeling and instrumental variable (IV) analyses. RESULTS: A total of 2,043 patients within the indicated area for 70-GS use were included, of whom 298 received a 70-GS. Without use of the 70-GS, 45% of patients received CT. The 70-GS use was associated with a 9.5% decrease in CT administration (95% confidence interval (CI): -15.7 to -3.3%) in linear mixed-effect model analyses and IV analyses showed similar results (-9.9%; 95% CI: -19.3 to -0.4). CONCLUSION: In patients in whom the Dutch national guidelines suggest the use of a gene-expression profile, 70-GS use is associated with a 10% decrease in the administration of adjuvant CT.Genet Med 18 7, 720-726.Genetics in Medicine (2016); 18 7, 720-726. doi:10.1038/gim.2015.152.

Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.

BACKGROUND: This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC). METHODS: Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry. RESULTS: A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these patients, respectively (P < 0.0001). Breast-conserving surgery was performed for 24.4 % of the patients with ILC receiving NAC versus 39.4 % of the patients with IDC. In the ILC group, 8.2 % of the patients needed surgical reinterventions after BCS due to tumor-positive resection margins compared with 3.4 % of the patients with IDC (P < 0.0001). Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC. CONCLUSION: The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.

Patients with invasive lobular breast cancer are less likely to undergo breast-conserving surgery: a population based study in the Netherlands.

PURPOSE: The aim of this study was to compare the frequency of breast-conserving surgery (BCS) between early-stage invasive ductal (IDC) and invasive lobular breast cancer (ILC). METHODS: Women with primary non-metastatic pT1 and pT2 IDC or ILC diagnosed between 1990 and 2010 were selected from the NCR. All patients underwent BCS or primary mastectomy without neoadjuvant treatment and proportions per year were calculated. Logistic regression analysis with adjustment for period, age, nodal status and tumor size was performed to determine the impact of histology on the likelihood of undergoing BCS. RESULTS: A total of 152,574 patients underwent surgery in the period between 1990 and 2010, of which 89 % had IDC and 11 % had ILC. In the group of IDC with pT1 and pT2 tumors combined, 54 % underwent BCS compared with 43 % of patients with ILC (p < 0.0001). The proportion of patients with IDC treated by BCS increased from 46 % in 1990 to 62 % in 2010. The BCS rate among ILC patients increased from 39 % in 1990 to 48 % in 2010. Patients with ILC were less likely to undergo BCS compared with patients with IDC (odds ratio 0.69; 95 % confidence interval 0.66-0.71). CONCLUSION: The incidence of BCS for patients with IDC or ILC is rising in The Netherlands. However, the increase of BCS is less explicit in patients with ILC, with a higher chance of undergoing mastectomy compared with patients with IDC.

The Value of Ipsilateral Breast Tumor Recurrence as a Quality Indicator: Hospital Variation in the Netherlands.

PURPOSE: All Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5 %. This study determined the value of IBTR as an indicator to compare quality of care between hospitals. METHODS: All patients with breast cancer (pT1-3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated by using the Kaplan-Meier method. Hospital variation was presented in funnel plots. Multivariate analysis was used to assess hospital characteristics associated with IBTR rates. RESULTS: A total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85 % (95 % confidence interval 2.68-3.03) and was significantly lower for BCS than for mastectomy (2.38 vs. 3.45 %, p < 0.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70 % between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5 %. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates. CONCLUSIONS: Our population-based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value.

Outcomes of a population-based series of early breast cancer patients with micrometastases and isolated tumour cells in axillary lymph nodes.

BACKGROUND: Axillary lymph node staging is traditionally important to provide prognostic information to guide further treatment. However, the relevance of isolated tumour cells (ITC) or micrometastases in axillary nodes and the need for adjuvant treatment remain uncertain. PATIENTS AND METHODS: Data from 18 370 patients with pT1-2 breast cancer with pN0, pN0i+ or pN1mi were analysed. The primary end point was 5-year disease-free survival (locoregional recurrence, distant metastases or contralateral breast cancer). RESULTS: Five-year disease-free survival was 89.9% [95% confidence interval 89.5% to 90.4%]; and did not differ significantly between groups. After adjusting for prognostic factors (including treatment), patients with ITC had a comparable risk (hazard ratio = 1.12) as patients with node-negative disease, while patients with micrometastases had a 38% higher risk of recurrence. CONCLUSION(S): Patients with ITC and node-negative breast cancer appear to have similar prognosis, and those with micrometastases have a 38% higher risk of tumour recurrence. However, considering that disease-free survival is already high, we are reluctant to advise chemotherapy in all patients with ITC or micrometastases. In future, genomic tumour characteristics might predict the propensity of dissemination from the primary cancer better than the status of the axillary lymph nodes.

Chronic fatigue in childhood cancer survivors is associated with lifestyle and psychosocial factors; a DCCSS LATER study.

BACKGROUND: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). PATIENTS AND METHODS: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. RESULTS: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37). CONCLUSION: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS.

Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer.

BACKGROUND: On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. PATIENTS AND METHODS: Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50-70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy. RESULTS: In total, 19,609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P < 0.0001). In lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64-0.76; P < 0.0001], compared with hormonal treatment alone. The HR in lobular cancer was 1.00 (95% CI 0.82-1.21; P = 0.97). CONCLUSION: Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.

Improved survival of patients with primary distant metastatic breast cancer in the period of 1995-2008. A nationwide population-based study in the Netherlands.

In this study, changes in prognosis for more than 8,000 patients with primary distant metastatic breast cancer were analyzed, using nation-wide data of the Netherlands Cancer Registry. Besides the roll of systemic treatment, the effect of surgery of the primary tumor was evaluated. Between 1995 and 2008, 160,595 new patients were diagnosed with invasive breast cancer. Of these patients, 8,031 (5.0%) had distant metastases at diagnosis. Patients were divided into three periods, based on the year of diagnosis of their disease. The median survival was 1.42 years for patients diagnosed in the period 1995-1999, 1.61 years in the period 2000-2004 and 1.95 years in the period 2005-2008. The improvement of the median survival was most pronounced for patients younger than 50 years. Patients receiving systemic treatment, loco-regional radiotherapy or breast surgery had a significantly lower risk of death compared to patients not receiving these treatments. An improvement of 6 months is observed in the median survival of patients with primary distant metastatic breast cancer between 1995 and 2008. The increased efficacy of chemotherapy and the introduction of targeted treatments are the most likely explanations for this improvement, which was most marked for younger patients.

Health-related quality of life in Dutch adult survivors of childhood cancer: A nation-wide cohort study.

AIM: To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL. METHODS: Adult CCS (age >18, diagnosed <18, ≥5 years since diagnosis) from the Dutch LATER registry completed the Medical Outcome Study Short Form 36 (SF-36) to measure HRQOL and provided sociodemographic characteristics. Age-adjusted mean SF-36 scale scores of CCS were compared to the Dutch general population for men and women separately using t-tests, with effect size d. Multivariate logistic regression models were built to identify sociodemographic and cancer-related risk factors for impaired physical and mental HRQOL. RESULTS: Both male and female CCS (N = 2301, mean age = 35.4 years, 49.6% female) reported significantly (p ≤ .005) worse HRQOL than the general population on almost all scales of the SF-36 (-.11 ≤ d ≤ -.56). Largest differences were found on vitality and general health perceptions. Significant risk factors (p ≤ .05) for impaired physical HRQOL were female sex, older age at diagnosis, not having a partner, low educational attainment, disease recurrence and exposure to radiotherapy, specifically to lower extremity radiation. Odds ratios (ORs) ranged from 1.6 to 3.7. Significant risk factors for impaired mental HRQOL were age 26-35 years, male sex, not having a partner and low educational attainment. ORs ranged from 1.3 to 2.0. CONCLUSION: Adult CCS had worse HRQOL than the general population. CCS most at risk were those with low educational attainment and without a partner. Adult CCS could benefit from routine surveillance of their HRQOL. Special attention for CCS' vitality and health perceptions and beliefs is warranted.

Site of childhood cancer care in the Netherlands.

BACKGROUND: Due to the complexity of diagnosis and treatment, care for children and young adolescents with cancer preferably occurs in specialised paediatric oncology centres with potentially better cure rates and minimal late effects. This study assessed where children with cancer in the Netherlands were treated since 2004. METHODS: All patients aged under 18 diagnosed with cancer between 2004 and 2013 were selected from the Netherlands Cancer Registry (NCR) and linked with the Dutch Childhood Oncology Group (DCOG) database. Associations between patient and tumour characteristics and site of care were tested statistically with logistic regression analyses. RESULTS: This population-based study of 6021 children diagnosed with cancer showed that 82% of them were treated in a paediatric oncology centre. Ninety-four percent of the patients under 10 years of age, 85% of the patients aged 10-14 and 48% of the patients aged 15-17 were treated in a paediatric oncology centre. All International Classification of Childhood Cancers (ICCC), 3rd edition, ICCC-3 categories, except embryonal tumours, were associated with a higher risk of treatment outside a paediatric oncology centre compared to leukaemia. Multivariable analyses by ICCC-3 category revealed that specific tumour types such as chronic myelogenous leukaemia (CML), embryonal carcinomas, bone tumours other type than osteosarcoma, non-rhabdomyosarcomas, thyroid carcinomas, melanomas and skin carcinomas as well as lower-staged tumours were associated with treatment outside a paediatric oncology centre. CONCLUSION: The site of childhood cancer care in the Netherlands depends on the age of the cancer patient, type of tumour and stage at diagnosis. Collaboration between paediatric oncology centre(s), other academic units is needed to ensure most up-to-date paediatric cancer care for childhood cancer patients at the short and long term.

Introduction of sentinel node biopsy and stage migration of breast cancer.

AIM: The purpose of this study was to examine in a large population based group of breast cancer patients treated in a regular care setting whether the introduction of the Sentinel Node Biopsy (SNB) led to detection of a higher percentage of patients with positive regional lymph nodes. METHODS: The study includes 3665 early breast cancer patients, aged 30-85 years, diagnosed in the period 1997-2002 and registered at the Regional Cancer Registry of the Comprehensive Cancer Centre Middle Netherlands. During this period the SNB was introduced. The outcome of staging was compared for groups staged with or without SNB. A logistic regression model was used to adjust for age, calendar period and tumour size. RESULTS: Overall a quarter of all patients over the period 1997-2002 underwent a SNB as method of lymphatic staging. The use of SNB clearly increased over time: from 2% in 1998 to 65% in 2002. The percentage node positive patients also rose significantly; before introduction of the SNB 30% of all patients were diagnosed with positive lymph nodes, and after SNB introduction this percentage was 40%. The increase is largely explained by the increase of patients diagnosed with only micrometastases. Adjustment did not change the results. CONCLUSION: In conclusion, introduction of the SNB in early breast cancer led to significant upstaging of breast cancer patients treated in a regular care setting, due to the detection of more micrometastases. Since the relevance of micrometastases for long term survival is not yet known, this upstaging potentially led to over treatment of patients. On the other side, for some patients axillary lymph node dissection was prevented by the SNB procedure, preventing comorbidity.

Contemporary risks of local and regional recurrence and contralateral breast cancer in patients treated for primary breast cancer.

INTRODUCTION: Breast cancer treatment has evolved extensively over the past two decades with a shift towards less invasive local treatment and increased systemic treatment. The present study aimed to investigate the rates of local (LR) and regional (RR) recurrence and contralateral breast cancer (CBC), evaluating the influence of contributing factors. MATERIALS AND METHODS: We selected all female patients operated for unilateral primary breast cancer (anyTN, M0) between 2003 and 2008 from the Netherlands Cancer Registry. The 5-year risks of developing LR, RR and CBC were estimated using Kaplan-Meier statistics. The influence of various patient, tumour and treatment characteristics was subsequently assessed in multivariable analyses. RESULTS: A total of 52,626 patients were identified. The rates of LR, RR and CBC were 2.7%, 1.5% and 2.9%, respectively. The rates of LR and RR decreased significantly over time in the period 2003-2008, from 3.2% to 2.4% for LR and 1.8 to 1.3% for RR, both becoming lower than the risk of CBC of 2.8%. Multivariable analysis showed that age, tumour size, lymph node involvement, tumour histologic type, grade and hormone receptor status were significant prognosticators for LR and RR, but not for CBC. A trend towards a beneficial effect of breast conserving surgery on LR and RR was seen, while systemic therapy proved to have a protective effect on all three end-points. CONCLUSIONS: In breast cancer patients treated between 2003 and 2008 locoregional recurrence rates decreased and have ended up lower than the risk of developing CBC.

Survival of breast cancer patients with synchronous or metachronous central nervous system metastases.

BACKGROUND: Central nervous system (CNS) metastases represent a devastating complication for advanced breast cancer patients. This observational study examines the influence of patient, tumour and treatment characteristics on overall survival after synchronous or metachronous CNS metastases. METHODS: Information on 992 breast cancer patients with CNS metastases (whose primary tumour was diagnosed between 2004 and 2010) was retrieved from the Netherlands Cancer Registry (NCR). Overall survival was calculated from the date of CNS metastatic diagnosis, and the impact of prognostic factors on survival was assessed using univariate and multivariate extended Cox-regression models. RESULTS: We identified 165 patients with synchronous and 827 patients with metachronous CNS metastases. The majority of patients (88%) presented with brain metastases only, 12% had leptomeningeal metastases. Overall median survival was 5.0 months. Non-triple-negative breast cancer and systemic therapy were associated with improved survival in both groups. In patients with synchronous CNS metastases, surgery for the primary tumour and the metastases also improved survival. In patients with metachronous metastases, younger age (<50 years), lower initial tumour stage (I), ductal carcinoma, a prolonged time interval until diagnosis of CNS metastasis (>1 year), and absence of extracranial metastases were associated with improved survival. Metastasectomy and radiation therapy did not provide benefit beyond the first six months. CONCLUSIONS: No difference in survival was established between synchronous and metachronous CNS metastases. Triple-negative disease is prognostically unfavourable in both groups, while those receiving treatment have a better outcome. Metastasectomy and radiotherapy improve survival within the first six months, and additional benefit may be derived from systemic therapy.

Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients: Identification rate and influence on axillary treatment.

The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The Netherlands. Patients diagnosed with clinically node negative primary breast cancer between 1st January 2010 and 30th June 2013 who received NAC and SNB were selected from the Netherlands Cancer Registry. Data on patient and tumour characteristics, axillary staging and treatment were analysed. Two groups were defined: (1) patients with SNB before NAC (N=980) and (2) patients with SNB after NAC (N=203). Eighty-three percent of patients underwent SNB before NAC, with large regional variation (35-99%). The SN identification rate differed for SNBs conducted before and after NAC (98% versus 95%; p=0.032). A lower proportion of patients had a negative SNB when assessed before NAC compared to after (54% versus 67%; p=0.001). The proportion of patients receiving any axillary treatment was higher for those with SNB before NAC than after (45% versus 33%; p=0.006). In conclusion, variation exists in the timing of SNB in clinical practice in The Netherlands for clinically node negative breast cancer patients receiving NAC. The post-NAC SN procedure is, despite some lower SN identification rate, associated with a significantly less frequent axillary treatment and thus with less expected morbidity. The effect on recurrence rate is not yet clear. Patients in this registry will be followed prospectively for long-term outcome.

Incidence of primary malignant orbital tumours in the Netherlands.

AIMS: To describe the incidence and relative frequencies of primary malignant orbital tumours in the Netherlands from 1989 to 2006. METHODS: All registered primary malignant orbital tumours were extracted from the population-based database of the Netherlands Cancer Registry. Age-adjusted incidence of malignant orbital tumours per 10,000,000 persons per year and the estimated annual percentage change (EAPC) were computed. RESULTS: A total of 367 malignant orbital tumours were registered. The average age-adjusted incidence of malignant orbital tumours is 10.9. Lymphoma has a relative frequency of 67%, rhabdomyosarcoma 12%, adenocarcinoma 6%, and adenoid cystic carcinoma 5%. The incidence of primary malignant orbital tumours has been increasing in the Netherlands (EAPC +2.8%). CONCLUSION: In the Netherlands, lymphoma is the most common primary malignant orbital tumour, followed by rhabdomyosarcoma, adenocarcinoma, and adenoid cystic carcinoma. The relative frequencies of the different histological tumour types are comparable to the frequencies in other parts of the world. The incidence of malignant primary orbital tumours shows a slight increase between 1989 and 2006.

Axillary recurrence rate after tumour negative and micrometastatic positive sentinel node procedures in breast cancer patients, a population based multicenter study.

BACKGROUND: The sentinel lymph node procedure is a widely accepted method for staging of patients with early breast cancer. This study evaluates the incidence of axillary relapse after negative sentinel node biopsy in the seven hospitals in the central part of the Netherlands. METHODS: This study concerns all patients with a T1-2 breast carcinoma who were staged with a sentinel lymph node biopsy in one of the hospitals in the region. Patients with a tumour-free sentinel node without additional axillary lymph node dissection and patients with a sentinel node containing micrometastases were prospectively included and data concerning tumour and primary treatment were recorded. After a median follow-up period of 46 months supplementary data were collected of all patients. RESULTS: Between January 2002 and December 2003, 541 patients underwent a sentinel node biopsy of which the sentinel node was negative for metastatic disease. During the follow-up period three patients were diagnosed with an axillary recurrence. The incidence of axillary relapse after tumour negative sentinel node biopsy in this study is 0.6% (3/541). In 23 patients a distant metastasis developed. An event occurred in 11% of the patients with a micrometastasis in the sentinel node. This was not significantly different from the patients with a tumour-free sentinel node. CONCLUSION: The results suggest that the sentinel lymph node procedure as performed in the region Middle Netherlands is a reliable and accurate instrument for staging of patients with early breast cancer. In our study we observed a non-significant different risk of distant disease in case of micrometastases compared to a tumour negative sentinel node.