A.B.G. Kwast

A validated web-based nomogram for predicting positive surgical margins following breast-conserving surgery as a preoperative tool for clinical decision-making

BACKGROUND Breast-conserving therapy, consisting of lumpectomy and adjuvant radiotherapy, is considered standard treatment for early-stage breast cancer. One of the most important risk factors of local recurrence is the presence of positive surgical margins following lumpectomy. We aimed to develop and validate a predictive model (nomogram) to predict for positive margins following the first attempt at lumpectomy as a preoperative tool for clinical decision-making. METHODS Patients with clinical T1-2N0-1Mx-0 histology-proven invasive breast carcinoma who underwent BCT throughout the North-East region of The Netherlands between June 2008 and July 2009 were selected from the Netherlands Cancer Registry (n = 1185). Results from multivariate logistic regression analyses served as the basis for development of the nomogram. Nomogram calibration and discrimination were assessed graphically and by calculation of a concordance index, respectively. Nomogram performance was validated on an external independent dataset (n = 331) from the University Medical Center Groningen. RESULTS The final multivariate regression model included clinical, radiological, and pathological variables. Concordance indices were calculated of 0.70 (95% CI: 0.66-0.74) and 0.69 (95% CI: 0.63-0.76) for the modeling and the validation group, respectively. Calibration of the model was considered adequate in both groups. A nomogram was developed as a graphical representation of the model. Moreover, a web-based application (http://www.breastconservation.com) was build to facilitate the use of our nomogram in a clinical setting. CONCLUSION We developed and validated a nomogram that enables estimation of the preoperative risk of positive margins in breast-conserving surgery. Our nomogram provides a valuable tool for identifying high-risk patients who might benefit from preoperative MRI and/or oncoplastic surgery.

Breast cancer follow-up: from the perspective of health professionals and patients

Increased breast cancer incidence and better survival have raised the number of patients requiring follow-up care. Despite guidelines, there is controversy about appropriate breast cancer follow-up. Therefore, semi-structured interviews were conducted in two hospitals with 23 patients and 18 health professionals (HPs) in order to explore opinions and preferences about the purpose, the duration and frequency of breast cancer follow-up and which examinations should be done, by whom. The transcripts were inductively analysed and coded into pre-identified themes. Patients were followed more intensively than guidelines recommend. HPs mentioned three major reasons; patient preferences, each discipline wanting to observe the patient, and financial incentives. For patients and HPs the most important purpose of follow-up was early detection of new malignancies. A highly valued aspect of follow-up mentioned by HPs was the psychosocial support, which was rarely mentioned by patients. Patients expectations about the benefits of follow-up and additional examinations were sometimes unrealistic. Patients and HPs were positive about nurse practitioner-led follow-up, but less positive about general practitioner-led follow-up. Important barriers to current guideline adherence were revealed and should be taken into account by implementing new individualised guidelines. Furthermore, patients should be better informed about the benefits of follow-up to prevent unrealistic expectations.

Availability of stage at diagnosis, cancer treatment delay and compliance with cancer guidelines as cancer registry indicators for cancer care in Europe: Results of EUROCHIP-3 survey

EUROCHIP (European Cancer Health Indicators Project) focuses on understanding inequalities in the cancer burden, care and survival by the indicators “stage at diagnosis,” “cancer treatment delay” and “compliance with cancer guidelines” as the most important indicators. Our study aims at providing insight in whether cancer registries collect well‐defined variables to determine these indicators in a comparative way. Eighty‐six general European population‐based cancer registries (PBCR) from 32 countries responded to the questionnaire, which was developed by EUROCHIP in collaboration with ENCR (European Network of Cancer Registries) and EUROCOURSE. Only 15% of all the PBCR in EU had all three indicators available. The indicator “stage at diagnosis” was gathered for at least one cancer site by 81% (using TNM in 39%). Variables for the indicator “cancer treatment delay” were collected by 37%. Availability of type of treatment (30%), surgery date (36%), starting date of radiotherapy (26%) and starting date of chemotherapy (23%) resulted in 15% of the PBCRs to be able to gather the indicator “compliance to guidelines”. Lack of data source access and qualified staff were the major reasons for not collecting all the variables. In conclusion, based on self‐reporting, a few of the participating PBCRs had data available which could be used for clinical audits, evaluation of cancer care projects, survival and for monitoring national cancer control strategies. Extra efforts should be made to improve this very efficient tool to compare cancer burden and the effects of the national cancer plans over Europe and to learn from each other.

Survival after Locoregional Recurrence or Second Primary Breast Cancer: Impact of the Disease-Free Interval

The association between the disease-free interval (DFI) and survival after a locoregional recurrence (LRR) or second primary (SP) breast cancer remains uncertain. The objective of this study is to clarify this association to obtain more information on expected prognosis. Women first diagnosed with early breast cancer between 2003–2006 were selected from the Netherlands Cancer Registry. LRRs and SP tumours within five years of first diagnosis were examined. The five-year period was subsequently divided into three equal intervals. Prognostic significance of the DFI on survival after a LRR or SP tumour was determined using Kaplan-Meier estimates and multivariable Cox regression analysis. Follow-up was complete until January 1, 2014. A total of 37,278 women was included in the analysis. LRRs or SP tumours were diagnosed in 890 (2,4%) and 897 (2,4%) respectively. Longer DFI was strongly and independently related to an improved survival after a LRR (long versus short: HR 0.65, 95% CI 0.48–0.88; medium versus short HR 0.81, 95% CI 0.65–1.01). Other factors related to improved survival after LRR were younger age (<70 years) and surgical removal of the recurrence. No significant association was found between DFI and survival after SP tumours. This is the first study to explore the association between the DFI and survival after recurrence in a nationwide population-based cancer registry. The DFI before a LRR is an independent prognostic factor for survival, with a longer DFI predicting better prognosis.

Increased risks of third primary cancers of non-breast origin among women with bilateral breast cancer

Background:This study examined the risk of third cancer of non-breast origin (TNBC) among women with bilateral breast cancer (BBC; either synchronous or metachronous), focussing on the relation with breast cancer treatment.Methods:Risk was assessed, among 8752 Dutch women diagnosed with BBC between 1989 and 2008, using standardised incidence ratios (SIR) and Cox regression analyses to estimate the hazard ratio (HR) of TNBC for different treatment modalities.Results:Significant increased SIRs were observed for all TNBCs combined, haematological malignancies, stomach, colorectal, non-melanoma skin, lung, head and neck, endometrial, and ovarian cancer. A 10-fold increased risk was found for ovarian cancer among women younger than 50 years (SIR=10.0, 95% confidence interval (CI)=5.3–17.4). Radiotherapy was associated with increased risks of all TNBCs combined (HR=1.3; 95%CI=1.1–1.6, respectively). Endocrine therapy was associated with increased risks of all TNBCs combined (HR=1.2; 95%CI=1.0–1.5), haematological malignancies (HR=2.0; 95%CI=1.1–3.9), and head and neck cancer (HR=3.3; 95%CI=1.1–10.4). After chemotherapy decreased risks were found for all TNBCs combined (HR=0.63; 95%CI=0.5–0.87).Conclusion:Increased risk of TNBC could be influenced by genetic factors (ovarian cancer) or an effect of treatment (radiotherapy and endocrine therapy). More insight in the TNBC risk should further optimise and individualise treatment and surveillance protocols in (young) women with BBC.

Attending the breast screening programme after breast cancer treatment: a population-based study

INTRODUCTION In the Netherlands, breast cancer patients are treated and followed at least 5 years after diagnosis. Furthermore, all women aged 50-74 are invited biennially for mammography by the nationwide screening programme. The relation between the outpatient follow-up (follow-up visits in the outpatient clinic for 5 years after treatment) and the screening programme is not well established and attending the screening programme as well as outpatient follow-up is considered undesirable. This study evaluates potential factors influencing women to attend the screening programme during their outpatient follow-up (overlap) and the (re-)attendance to the screening programme after 5 years of outpatient follow-up. METHODS Data of breast cancer patients aged 50-74 years, treated for primary breast cancer between 1996 and 2007 were selected from the Netherlands Cancer Registry and linked to the National Breast Cancer Screening Programme in the Northern region. Cox regression analyses were used to study women (re-)attending the screening programme over time, possible overlap with the outpatient follow-up and factors influencing this. RESULTS In total 11227 breast cancer patients were included, of whom 19% attended the screening programme after breast cancer treatment, 4.4% within 5 years and 15.4% after more than 5 years. Factors that independently influenced attendance within 5 years as well as more than 5 years after treatment were: interval tumours (HR 0.77; 95%CI 0.61-0.97 and HR 0.69; 95%CI 0.53-0.88, ref: screen-detected tumours), receiving adjuvant radiotherapy (HR 0.65; 95%CI 0.47-0.90 and HR 0.66; 95%CI 0.47-0.93; ref: none) and diagnosis of in situ tumours (HR 1.67; 95%CI 1.25-2.23 and HR 1.39; 95%CI 1.05-1.85; ref: stage I tumours). Non-screen related tumours (HR 0.41; 95%CI 0.29-0.58) and recent diagnosis (HR 0.89 per year; 95%CI 0.86-0.92) were only associated with attendance within 5 years after treatment. CONCLUSION The interrelation between outpatient follow-up and screening should be improved to avoid overlap and low attendance to the screening programme after outpatient follow-up. Breast cancer patients should be informed that attending the screening programme during the outpatient follow-up is not necessary.

Survival After Locoregional Recurrence or Second Primary Breast Cancer: Impact of the Disease-Free Interval

The association between the disease-free interval (DFI) and survival after a locoregional recurrence (LRR) or second primary (SP) breast cancer remains uncertain. The objective of this study is to clarify this association to obtain more information on expected prognosis. Women first diagnosed with early breast cancer between 2003–2006 were selected from the Netherlands Cancer Registry. LRRs and SP tumours within five years of first diagnosis were examined. The five-year period was subsequently divided into three equal intervals. Prognostic significance of the DFI on survival after a LRR or SP tumour was determined using Kaplan-Meier estimates and multivariable Cox regression analysis. Follow-up was complete until January 1, 2014. A total of 37,278 women was included in the analysis. LRRs or SP tumours were diagnosed in 890 (2,4%) and 897 (2,4%) respectively. Longer DFI was strongly and independently related to an improved survival after a LRR (long versus short: HR 0.65, 95% CI 0.48–0.88; medium versus short HR 0.81, 95% CI 0.65–1.01). Other factors related to improved survival after LRR were younger age (<70 years) and surgical removal of the recurrence. No significant association was found between DFI and survival after SP tumours. This is the first study to explore the association between the DFI and survival after recurrence in a nationwide population-based cancer registry. The DFI before a LRR is an independent prognostic factor for survival, with a longer DFI predicting better prognosis