M. Moossdorff

Bio: M. Moossdorff is an academic researcher from Maastricht University. The author has contributed to research in topics: Breast cancer & Cancer registry. The author has an hindex of 9, co-authored 20 publications receiving 370 citations. Previous affiliations of M. Moossdorff include Maastricht University Medical Centre.

The role of MRI in axillary lymph node imaging in breast cancer patients: a systematic review.

Abstract: Objectives To assess whether MRI can exclude axillary lymph node metastasis, potentially replacing sentinel lymph node biopsy (SLNB), and consequently eliminating the risk of SLNB-associated morbidity.

Maastricht Delphi consensus on event definitions for classification of recurrence in breast cancer research.

Abstract: Summary of the consensus on the definition of local event, second primary breast cancer, regional event, and distant event for classification of recurrence in breast cancer research Term Definition Local event(after mastectomy or breast conserving therapy)Any epithelial breast cancer or DCIS in ipsilateral breast tissueBreast cancer in surgical scarBreast cancer in biopsy tractBreast cancer in skin and subcutaneous tissue on the (former) ipsilateral breast and ipsilateral thoracic wall* Should NOT include: LCIS, phyllodes tumors, any benign breast lesion, any breast cancer event involving the sternal boneSecond primary breast cancer Any epithelial breast cancer in the contralateral breast (with or without lymph node metastases on that side)Regional event Breast cancer in ipsilateral axillary, infraclavicular, supraclavicular, internal mammary/ parasternal, or intramammary lymph nodeDistant event Breast cancer in any organ other than breast, excluding the items listed under local event, second primary breast cancer, and regional event.Therefore also including any breast cancer event involving the sternal boneTherefore also including breast cancer in contralateral lymph nodes (axillary, infraclavicular, supraclavicular, and internal mammary), in absence of synchronous ipsilateral or contralateral breast malignancy or distant metastasisTissue samplingPathology confirmation (histology or cytology) of a first, solitary lesion suspected for metastasis is highly recommended if feasible; if tissue sampling is impossible, unconfirmed metastasis is acceptable at discretion of the treating physicianMultiple lesions consistent with metastases on imaging are acceptable without pathology confirmation

Clinical tumor stage is the most important predictor of pathological complete response rate after neoadjuvant chemotherapy in breast cancer patients

Abstract: Pathological complete response (pCR) is the ultimate response in breast cancer patients treated with neoadjuvant chemotherapy (NCT). It might be a surrogate outcome for disease-free survival (DFS) and overall survival (OS). We studied the effect of clinical tumor stage (cT-stage) on tumor pCR and the effect of pCR per cT-stage on 5-year OS and DFS. Using the Netherlands Cancer Registry, all primary invasive breast cancer patients treated with NCT from 2005 until 2008 were identified. Univariable logistic regression analysis was performed to evaluate the effect of cT-stage on pCR, stepwise logistic regression analysis to correct for potential confounders and Kaplan–Meier survival analyses to calculate OS and DFS after five years. In 2366 patients, overall pCR rate was 21%. For cT1, cT2, cT3, and cT4, pCR rates were 31, 22, 18, and 17%, respectively. Lower cT-stage (cT1-2 vs cT3-4) was a significant independent predictor of higher pCR rate (p < 0.001, OR 3.15). Furthermore, positive HER2 status (p < 0.001, OR 2.30), negative estrogen receptor status (p = 0.062, OR 1.69), and negative progesterone receptor status (p = 0.008, OR 2.27) were independent predictors of pCR. OS and DFS were up to 20% higher in patients with cT2-4 tumors with pCR versus patients without pCR. DFS was also higher for cT1 tumors with pCR. The most important predictor of pCR in breast cancer patients is cT-stage: lower cT-stages have significantly higher pCR rates than higher cT-stages. Patients with cT2-4 tumors achieving pCR have higher OS and DFS compared to patients not achieving pCR.

Contralateral lymph node recurrence in breast cancer: Regional event rather than distant metastatic disease. A systematic review of the literature

Abstract: Aims After treatment for breast cancer, some patients experience a contralateral lymph node recurrence (CLNR). Traditionally, contralateral nodes are considered a distant site. However, aberrant lymph drainage after previous surgery is common. This might indicate that CLNR is a regional event. This study aimed to review the literature to determine prognosis after CLNR. Methods PubMed was searched up until July 2014. Articles on CLNR with or without ipsilateral breast tumour recurrence (IBTR), and repeat sentinel node (SN) studies reporting on positive contralateral nodes were included. Exclusion criteria were synchronous contralateral breast cancer and synchronous distant events. Results 24 articles were included, describing 48 patients. Of these 48, 26 patients had an isolated CLNR, 7 IBTR and clinically detected CLNR, and 15 IBTR with a positive contralateral repeat SN. Isolated CLNR occurred earlier (45.9 months) than IBTR with CLNR (126.6 months, p Conclusions Although observed in a small population, the survival of CLNR is not comparable to distant disease. Most patients received locoregional and systemic treatment suggesting a curative approach. This indicates that CLNR should be regarded as a regional event.

10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study

Abstract: Summary Background Investigators of registry-based studies report improved survival for breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer. As these studies did not present long-term overall and breast cancer-specific survival, the effect of breast-conserving surgery plus radiotherapy might be overestimated. In this study, we aimed to evaluate 10 year overall and breast cancer-specific survival after breast-conserving surgery plus radiotherapy compared with mastectomy in Dutch women with early breast cancer. Methods In this population-based study, we selected all women from the Netherlands Cancer Registry diagnosed with primary, invasive, stage T1–2, N0–1, M0 breast cancer between Jan 1, 2000, and Dec 31, 2004, given either breast-conserving surgery plus radiotherapy or mastectomy, irrespective of axillary staging or dissection or use of adjuvant systemic therapy. Primary outcomes were 10 year overall survival in the entire cohort and breast cancer-specific survival in a representative subcohort of patients diagnosed in 2003 with characteristics similar to the entire cohort. We estimated breast cancer-specific survival by calculating distant metastasis-free and relative survival for every tumour and nodal category. We did multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs) for overall and distant metastasis-free survival. We estimated relative survival by calculating excess mortality ratios using life tables of the general population. We did multiple imputation to account for missing data. Findings Of the 37 207 patients included in this study, 21 734 (58%) received breast-conserving surgery plus radiotherapy and 15 473 (42%) received mastectomy. The 2003 representative subcohort consisted of 7552 (20%) patients, of whom 4647 (62%) received breast-conserving surgery plus radiotherapy and 2905 (38%) received mastectomy. For both unadjusted and adjusted analysis accounting for various confounding factors, breast-conserving surgery plus radiotherapy was significantly associated with improved 10 year overall survival in the whole cohort overall compared with mastectomy (HR 0·51 [95% CI 0·49–0·53]; p Interpretation Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer. Funding None.

Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173 797 patients

Abstract: Objectives To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy. Design Prospective nationwide population based study. Setting Nationwide Netherlands Cancer Registry. Participants Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173 797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80 228) and 2006-12 (n=93 569). Main outcome measures Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately. Results Compared with 1999-2005, patients from 2006-12 had smaller (≤T1 65% (n=60 570) v 60% (n=48 031); P<0.001), more often lymph node negative (N0 68% (n=63 544) v 65% (n=52 238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56 402) v 53% (n=42 185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32). Conclusions Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vital

A comprehensive literatures update of clinical researches of superparamagnetic resonance iron oxide nanoparticles for magnetic resonance imaging

Abstract: This paper aims to update the clinical researches using superparamagnetic iron oxide (SPIO) nanoparticles as magnetic resonance imaging (MRI) contrast agent published during the past five years. PubMed database was used for literature search, and the search terms were (SPIO OR superparamagnetic iron oxide OR Resovist OR Ferumoxytol OR Ferumoxtran-10) AND (MRI OR magnetic resonance imaging). The literature search results show clinical research on SPIO remains robust, particularly fuelled by the approval of ferumoxytol for intravenously administration. SPIOs have been tested on MR angiography, sentinel lymph node detection, lymph node metastasis evaluation; inflammation evaluation; blood volume measurement; as well as liver imaging. Two experimental SPIOs with unique potentials are also discussed in this review. A curcumin-conjugated SPIO can penetrate brain blood barrier (BBB) and bind to amyloid plaques in Alzheime’s disease transgenic mice brain, and thereafter detectable by MRI. Another SPIO was fabricated with a core of Fe3O4 nanoparticle and a shell coating of concentrated hydrophilic polymer brushes and are almost not taken by peripheral macrophages as well as by mononuclear phagocytes and reticuloendothelial system (RES) due to the suppression of non-specific protein binding caused by their stealthy ‘‘brush-afforded’’ structure. This SPIO may offer potentials for the applications such as drug targeting and tissue or organ imaging other than liver and lymph nodes.

[Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients].

Abstract: OBJECTIVE To assess influence of stage at breast cancer diagnosis, tumour biology, and therapy on survival in contemporary times of better (neo-)adjuvant systemic therapy. DESIGN Prospective nationwide population based study. METHOD Female primary breast cancer patients diagnosed between 1999 and 2012 (173,797). Participants were subdivided into two time cohorts on the basis of breast cancer diagnosis; 1999 through 2005 (n = 80,228) and 2006 through 2012 (n = 93,569). Main outcome measures were relative survival, compared between both cohorts, and the influence of traditional prognostic factors on overall mortality, analyzed with Cox regression for both cohorts separately. RESULTS Compared to 1999-2005 patients from 2006-2012 had smaller ( ≤ T1 65 vs. 60%; p < 0.001), more often lymph node negative (N0 68 vs. 65%; p < 0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60 vs. 53%; p < 0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-2012. Relative 5-years survival rate was 96% in 2006-2012, improved in all tumour and nodal stages compared to 1999-2005, and 100% in tumours ≤ 1 cm. With multivariable analyses, adjusted for age and tumour type, overall mortality decreased by surgery (especially breast conserving), radiotherapy and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-2012 T1c vs. T1a HR 1.54, 95% CI 1.33 to 1.78), but without significant difference in invasive breast cancers until 1 cm (2006-2012 T1b vs. T1a HR 1.04, 95% CI 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-2012 N1 vs. N0 HR 1.25, 95% CI 1.17 to 1.32). CONCLUSION Tumour stage at breast cancer diagnosis influences overall survival significantly also in the current era of effective systemic therapy. Early tumour stage at breast cancer diagnosis remains vital.

Preoperative prediction of sentinel lymph node metastasis in breast cancer by radiomic signatures from dynamic contrast‐enhanced MRI

Abstract: Background Sentinel lymph node (SLN) status is an important prognostic factor for patients with breast cancer, which is currently determined in clinical practice by invasive SLN biopsy. Purpose To noninvasively predict SLN metastasis in breast cancer using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) intra- and peritumoral radiomics features combined with or without clinicopathologic characteristics of the primary tumor. Study type Retrospective. Population A total of 163 breast cancer patients (55 positive SLN and 108 negative SLN). Field strength/sequence 1.5T, T1 -weighted DCE-MRI. Assessment A total of 590 radiomic features were extracted for each patient from both intratumoral and peritumoral regions of interest. To avoid overfitting, the dataset was randomly separated into a training set (∼67%) and a validation set (∼33%). The prediction models were built with the training set using logistic regression on the most significant radiomic features in the training set combined with or without clinicopathologic characteristics. The prediction performance was further evaluated in the independent validation set. Statistical tests Mann-Whitney U-test, Spearman correlation, least absolute shrinkage selection operator (LASSO) regression, logistic regression, and receiver operating characteristic (ROC) analysis were performed. Results Combining radiomic features with clinicopathologic characteristics, six features were automatically selected in the training set to establish the prediction model of SLN metastasis. In the independent validation set, the area under ROC curve (AUC) was 0.869 (NPV = 0.886). Using radiomic features alone in the same procedure, 4 features were selected and the validation set AUC was 0.806 (NPV = 0.824). Data conclusion This is the first attempt to demonstrate the feasibility of using DCE-MRI radiomics to predict SLN metastasis in breast cancer. Clinicopathologic characteristics improved the prediction performance. This study provides noninvasive methods to evaluate SLN status for guiding further treatment of breast cancer patients, and can potentially benefit those with negative SLN, by eliminating unnecessary invasive lymph node removal and the associated complications, which is a step further towards precision medicine. Level of evidence 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:131-140.