M. Moossdorff

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.

A model to predict pathologic complete response of axillary lymph nodes to neoadjuvant chemo(immuno)therapy in patients with clinically node-positive breast cancer.

BACKGROUND Between 20% and 42% of patients with clinically node-positive breast cancer achieve a pathologic complete response (pCR) of axillary lymph nodes after neoadjuvant chemotherapy or immunotherapy, or both, (chemo[immuno]therapy). Hypothetically, axillary lymph node dissection (ALND) may be safely omitted in these patients. This study aimed to develop a model for predicting axillary pCR in these patients. PATIENTS AND METHODS We retrospectively identified patients with clinically node-positive breast cancer who were treated with neoadjuvant chemo(immuno)therapy and ALND between 2005 and 2012 in 5 hospitals. Patient and tumor characteristics, neoadjuvant chemo(immuno)therapy regimens, and pathology reports were extracted. Binary logistic regression analysis was used to predict axillary pCR with the following variables: age, tumor stage and type, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, and administration of taxane and trastuzumab. The model was internally validated by bootstrap resampling. The overall performance of the model was assessed by the Brier score and the discriminative performance by receiver operating characteristic (ROC) curve analysis. RESULTS A model was developed based on 291 patients and was internally validated with a scaled Brier score of 0.14. The area under the ROC curve of this model was 0.77 (95% confidence interval [CI], 0.71-0.82). At a cutoff value of predicted probability ≥ 0.50, the model demonstrated specificity of 88%, sensitivity of 43%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 75%. CONCLUSION This prediction model shows reasonable accuracy for predicting axillary pCR. However, omitting axillary treatment based solely on the nomogram score is not justified. Further research is warranted to noninvasively identify patients with axillary pCR.

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

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 < 0.001) or with a positive contralateral repeat SN (217.2, p = 0.02). Surgical treatment was described for 38 patients, and consisted of axillary lymph node dissection for 34 (89.5%). Information on adjuvant therapy was available for 27 patients, 21 (77.8%) received chemotherapy. Follow-up information after CLNR was available for 23 patients (47.9%). Mean follow-up was 50.3 months. Overall survival and disease-free survival were 82.6% [95% CI 67.1-98.1] and 65.2% [45.7-84.7] respectively at last follow-up. 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.

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.

PurposeThis project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation.MethodsPubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics.ResultsTwo hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly.ConclusionsConsensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.

Inconsistent selection and definition of local and regional endpoints in breast cancer research

Results in breast cancer research are reported using study endpoints. Most are composite endpoints (such as locoregional recurrence), consisting of several components (for example local recurrence) that are in turn composed of specific events (such as skin recurrence). Inconsistent endpoint selection and definition might lead to unjustified conclusions when comparing study outcomes. This study aimed to determine which locoregional endpoints are used in breast cancer studies, and how these endpoints and their components are defined.

Diagnostic performance of gadofosveset-enhanced axillary MRI for nodal (re)staging in breast cancer patients: results of a validation study

AIM To evaluate diagnostic performance of gadofosveset (GDF)-enhanced magnetic resonance imaging (MRI) in addition to T2-weighted (T2W) MRI for nodal (re)staging in newly diagnosed breast cancer patients. MATERIALS AND METHODS Ninety patients underwent axillary T2W- and GDF-MRI. Two radiologists independently scored each lymph node; first on T2W-MRI, subsequently adjusting their score on GDF-MRI. Diagnostic performance parameters were calculated on node-by-node and patient-by-patient validation with histopathology as the reference standard. Furthermore, learning curve analysis for reading GDF-MRI was performed. RESULTS In patient-by-patient validation, overall reader performances for T2W- and GDF-MRI were similar with area under the receiver operating characteristic curves (AUC) of 0.75 and 0.77 (p=0.731) for reader 1 and 0.79 and 0.72 (p=0.156) for reader 2. For node-by-node validation, AUC values of T2W- and GDF-MRI were 0.76 and 0.82 (p=0.018) and 0.77 and 0.77 (p=0.998) for reader 1 and 2. The AUC for reader 1 was 0.71 for first one-third of nodes evaluated, improving to 0.80 and 0.95 for the next and last one-third, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) improved from 38%, 89%, 56%, and 79% to 60%, 93%, 64%, and 92%. The AUC of reader 2 improved from 0.69 to 0.79. CONCLUSION The present study confirmed that GDF-MRI, in addition to T2W-MRI, has potential as a non-invasive method for nodal (re)staging in breast cancer.