Marjolein L. Smidt

Can the Memorial Sloan-Kettering Cancer Center Nomogram Predict the Likelihood of Nonsentinel Lymph Node Metastases in Breast Cancer Patients in The Netherlands?

BackgroundAccording to Dutch guidelines, an axillary lymph node dissection (ALND) is recommended whenever a sentinel lymph node (SLN) contains metastatic disease. However, only in approximately 50% of patients with metastatic disease in the SLN are additional nodal metastases detected in the completion ALND. To identify the individual patient’s risk for non-SLN metastases, a nomogram containing eight predictors was developed by the Breast Service of Memorial Sloan-Kettering Cancer Center (New York, NY). The aim of this study was to test the accuracy of the nomogram on a population of Dutch breast cancer patients.MethodsPatient, tumor, and SLN metastasis characteristics were collected for 222 consecutive patients who underwent a completion ALND. The data of the index and test populations were compared. A receiver operating characteristic curve was drawn, and the area under the curve was calculated to assess the discriminative power of the nomogram.ResultsEven though our patient population differed in many respects from the source population, the area under the receiver operating characteristic curve amounted to .77, a value very much comparable to the one found in the source population.ConclusionsThe nomogram provides a fairly accurate predicted probability for the likelihood of non-SLN metastases in a general population of breast cancer patients at a regional teaching hospital in The Netherlands. This suggests that the nomogram’s originally calculated predictive accuracy may be valid for patient populations that differ considerably from the population in which it was developed.

Axillary Recurrence After a Negative Sentinel NodeBiopsy for Breast Cancer: Incidence and Clinical Significance

BackgroundSentinel lymph node biopsy (SLNB) carries the inherent risk of approximately 5% false-negative sampling. Undetected tumor-positive nodes of clinical importance are those that lead to axillary recurrence. This survey aims at clarifying the extent of this problem in current practice and literature.MethodsIn a regional teaching hospital, 696 consecutive breast cancer patients underwent SLNB between January 1998 and July 2003, and data were entered in a prospective database. PubMed and the Cochrane library were searched for a systematic review of the literature. Thirteen studies dealt with the follow-up of a cohort of sentinel lymph node (SLN)-negative patients or presented a case report.ResultsThe SLN identification rate was 97.1%. The SLN was tumor free in 439 (65%) of the 676 patients. After a median follow-up of 26 months, axillary recurrence was detected in 2 of 439 patients 4 and 27 months after the SLNB. The incidence of clinically apparent false-negative SLNB is .46%. The systematic review resulted in 3184 SLNB-negative patients with a median follow-up of 25 months. Axillary recurrence occurred in eight patients after a median of 21 months. The axillary recurrence rate in the literature is .25%. One third of these patients present with synchronous systemic metastases.ConclusionsAxillary recurrences after a negative SLNB occur, but at a much lower rate than would be expected on the basis of historical figures and the false-negative SLN findings. The natural history of axillary relapse after negative SLNB resembles the locoregional recurrence of breast cancer.

Pre-treatment differences and early response monitoring of neoadjuvant chemotherapy in breast cancer patients using magnetic resonance imaging: a systematic review.

ObjectivesTo assess whether magnetic resonance imaging (MRI) can identify pre-treatment differences or monitor early response in breast cancer patients receiving neoadjuvant chemotherapy.MethodsPubMed, Cochrane library, Medline and Embase databases were searched for publications until January 1, 2012. After primary selection, studies were selected based on predefined inclusion/exclusion criteria. Two reviewers assessed study contents using an extraction form.ResultsIn 15 studies, which were mainly underpowered and of heterogeneous study design, 31 different parameters were studied. Most frequently studied parameters were tumour diameter or volume, Ktrans, Kep, Ve, and apparent diffusion coefficient (ADC). Other parameters were analysed in only two or less studies. Tumour diameter, volume, and kinetic parameters did not show any pre-treatment differences between responders and non-responders. In two studies, pre-treatment differences in ADC were observed between study groups. At early response monitoring significant and non-significant changes for all parameters were observed for most of the imaging parameters.ConclusionsEvidence on distinguishing responders and non-responders to neoadjuvant chemotherapy using pre-treatment MRI, as well as using MRI for early response monitoring, is weak and based on underpowered study results and heterogeneous study design. Thus, the value of breast MRI for response evaluation has not yet been established.Key Points• Few well-validated pre-treatment MR parameters exist that identify responders and non-responders.• Eligible studies showed heterogeneous study designs which hampered pooling of data.• Confounders and technical variations of MRI accuracy are not studied adequately.• Value of MRI for response evaluation needs to be established further.

Contrast enhanced mammography: Techniques, current results, and potential indications

Contrast enhanced mammography: Techniques, current results, and potential indications M.B.I. Lobbes *, M.L. Smidt , J. Houwers , V.C. Tjan-Heijnen , J.E. Wildberger a Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands Department of Surgical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands Department of Medical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands

‘Reconstruction: Before or after postmastectomy radiotherapy?’ A systematic review of the literature

OBJECTIVE The aim of this review is to investigate the effect of timing of the reconstruction and radiotherapy, with respect to complication rate and cosmetic outcome, with a special focus on the timing of the placement of the definite implant. METHODS PubMed was searched for publications between January 2000 and December 2012. Of 37 eligible studies, timing of reconstruction, type, and incidence of complications were recorded. First, we calculated the weighted mean including confidence intervals for complications and cosmetic outcome overall, and for the following subgroups: (1) Autologous reconstruction after radiotherapy; (2) Definite implant reconstruction after radiotherapy; (3) Autologous reconstruction before radiotherapy; (4) Definite implant reconstruction before radiotherapy. A second analysis was performed using only studies that directly compared group 1 versus 3 and 2 versus 4. RESULTS A large variation in complication rates (8.7-70.0%) and in acceptable cosmetic outcome (41.4-93.3%) was reported. The first analysis showed more complications and a higher revision rate if an implant reconstruction was performed after radiotherapy; for autologous reconstruction fibrosis occurred more often if reconstruction was applied first. The second analysis showed no significant differences in total complication rate. Only implant failure occurred more often if applied after radiotherapy (odds ratio (OR) 3.03 [1.59-5.77]). No differences were found in both patient and physician satisfaction. CONCLUSIONS A definite implant reconstruction placed before radiotherapy limits the rate of complications. For autologous reconstruction, less fibrosis is seen if reconstruction is performed after radiotherapy, but timing had no significant impact on total complication rate.

Noninvasive nodal staging in patients with breast cancer using gadofosveset-enhanced magnetic resonance imaging: a feasibility study.

ObjectivesThe objectives of this study were to evaluate whether the axillary lymph nodes show enhancement on magnetic resonance imaging (MRI) after gadofosveset administration, to assess the time to peak enhancement, and to determine the diagnostic performance of gadofosveset-enhanced MRI for axillary nodal staging. Materials and MethodsTen women whose conditions had been diagnosed with invasive breast cancer (>2 cm) underwent both nonenhanced and gadofosveset-enhanced 3-dimensional T1-weighted axillary MRI. Signal intensity of the axillary lymph nodes and different adjacent tissues was measured, and relative signal intensity (rSI) was calculated. A Wilcoxon signed rank test was used to compare results of rSI between different time intervals. A radiologist evaluated all lymph nodes with regard to size, morphologic features, and gadofosveset uptake. All MRI-depicted lymph nodes were matched with the lymph nodes that were removed during surgery. Nodal status was investigated by a pathologist. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of gadofosveset-enhanced MRI for axillary lymph node staging were calculated. ResultsAfter contrast administration, a significant signal increase was observed in the lymph nodes (P < 0.05). When compared with muscle or fat, rSI of the lymph nodes demonstrated a significant postcontrast peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds (P < 0.05). A total of 152 lymph nodes were harvested during sentinel lymph node biopsy or axillary lymph node dissection, of which 116 were matched with the lymph nodes that were depicted on MRI. Histopathological examination resulted in 21 macrometastases and 8 micrometastases. Using contrast-enhanced MRI, 20 lymph nodes were rated as true positive; 83 as true negative; 4 as false positive; and 9 as false negative. This resulted in an overall node-by-node sensitivity, specificity, PPV, and NPV of 69%, 95%, 83%, and 90%, respectively. If the micrometastases were excluded from the analysis, MRI showed a sensitivity of 86% and a specificity of 94%. Calculated PPV and NPV were 75% and 97%, respectively. ConclusionsThe axillary lymph nodes show enhancement on MRI after gadofosveset administration, with a peak enhancement between 11 minutes and 30 seconds and 20 minutes and 50 seconds. Diagnostic performance of gadofosveset-enhanced axillary lymph node imaging in patients with breast cancer is promising, but further studies need to confirm these results.

The Quality of Tumor Size Assessment by Contrast-Enhanced Spectral Mammography and the Benefit of Additional Breast MRI

Background - Contrast-enhanced spectral mammography (CESM) is a promising new breast imaging modality that is superior to conventional mammography for breast cancer detection. We aimed to evaluate correlation and agreement of tumor size measurements using CESM. As additional analysis, we evaluated whether measurements using an additional breast MRI exam would yield more accurate results. Methods - Between January 1st 2013 and April 1st 2014, 87 consecutive breast cancer cases that underwent CESM were collected and data on maximum tumor size measurements were gathered. In 57 cases, tumor size measurements were also available for breast MRI. Histopathological results of the surgical specimen served as gold standard in all cases. Results - The Pearsons correlation coefficients (PCC) of CESM versus histopathology and breast MRI versus histopathology were all >0.9, p<0.0001. For the agreement between measurements, the mean difference between CESM and histopathology was 0.03 mm. The mean difference between breast MRI and histopathology was 2.12 mm. Using a 2x2 contingency table to assess the frequency distribution of a relevant size discrepancy of >1 cm between the two imaging modalities and histopathological results, we did not observe any advantage of performing an additional breast MRI after CESM in any of the cases. Conclusion - Quality of tumor size measurement using CESM is good and matches the quality of these measurement assessed by breast MRI. Additional measurements using breast MRI did not improve the quality of tumor size measurements.

The diagnostic performance of sentinel lymph node biopsy in pathologically confirmed node positive breast cancer patients after neoadjuvant systemic therapy: A systematic review and meta-analysis

PURPOSE To provide a systematic review and meta-analysis of studies investigating sentinel lymph node biopsy after neoadjuvant systemic therapy in pathologically confirmed node positive breast cancer patients. METHODS Pubmed and Embase databases were searched until June 19th, 2015. All abstracts were read and data extraction was performed by two independent readers. A random-effects model was used to pool the proportion for identification rate, false-negative rate (FNR) and axillary pCR with 95% confidence intervals. Subgroup analyses affirmed potential confounders for identification rate and FNR. RESULTS A total of 997 abstracts were identified and eventually eight studies were included. Pooled estimates were 92.3% (90.8-93.7%) for identification rate, 15.1% (12.7-17.6%) for FNR and 36.8% (34.2-39.5%) for axillary pCR. After subgroup analysis, FNR is significantly worse if one sentinel node was removed compared to two or more sentinel nodes (23.9% versus 10.4%, p = 0.026) and if studies contained clinically nodal stage 1-3, compared to studies with clinically nodal stage 1-2 patients (21.4 versus 13.1%, p = 0.049). Other factors, including single tracer mapping and the definition of axillary pCR, were not significantly different. CONCLUSION Based on current evidence it seems not justified to omit further axillary treatment in every clinically node positive breast cancer patients with a negative sentinel lymph node biopsy after neoadjuvant systemic therapy.

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using breast MRI – a review of current knowledge

Abstract Background: Breast MRI is the most accurate method for evaluating treatment response in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods: In this review, the

Noninvasive nodal restaging in clinically node positive breast cancer patients after neoadjuvant systemic therapy: A systematic review

OBJECTIVE To provide a systematic review of studies comparing the diagnostic performance of noninvasive techniques and axillary lymph node dissection in the identification of initially node positive patients with pathological complete response of axillary lymph nodes to neoadjuvant systemic therapy. METHODS PubMed and Embase databases were searched until May 21st, 2014. First, duplicate studies were eliminated. Next, study abstracts were read by two readers to assess eligibility. Studies were selected based on predefined inclusion criteria. Of these, data extraction was performed by two readers independently. RESULTS Of the 987 abstracts that were considered for inclusion, four were eligible for final analysis, which included a total of 572 patients. The diagnostic performance of clinical examination, axillary ultrasound, breast MRI, whole body (18)F-FDG PET-CT, and a prediction model to identify patients with pathological complete response were investigated. Studies were often limited by small sample size. Furthermore, systemic therapy regimens and definitions of clinical and pathological complete response were variable, refraining further pooling of data. The reported positive predictive value of different techniques to identify patients with axillary pathological complete response after neoadjuvant systemic therapy varied between 40% and 100%. CONCLUSION At present, there is no accurate noninvasive restaging technique able to identify patients with complete axillary response after neoadjuvant systemic therapy.