Which patient- and physician-related factors are associated with guideline adherent initiation of adjuvant endocrine therapy? Results of the prospective multi-centre cohort study BRENDA II

Background

We analysed factors that might influence patients’ and physicians’ decisions against the initiation of guideline adherent adjuvant endocrine therapy (ET).

Methods

In a prospective multi-centre study, including four certified breast cancer centres in Germany, patients with primary breast cancer were included from 2009 to 2012. Patients completed a questionnaire prior to surgery, adjuvant therapy, and 6 months after adjuvant therapy. This questionnaire assessed health-related quality of life (QoL), psychiatric co-morbidity, demographic characteristics, and the intensity of fear for ET. Guideline adherence was classified based on an algorithm derived from international guidelines. The tumour board’s (TB) decisions against or for ET was documented. The TB was blinded regarding the guideline results.

Results

In 666 patients, adjuvant ET was indicated according to the guideline recommendations. The TB decided in 92.3 % (n = 615) of those that adjuvant ET was indicated. TB’s decision against ET was associated with the younger age of patients (OR = 0.5; 95 % CI 0.3–0.9) and poor QoL (OR = 1.7; 95 % CI 1.0–2.8). In 93 patients, ET was not indicated according to the guidelines, and the TB decided in 84 of those not to prescribe ET. The TB decided in 93.4 % of the cases according to the guidelines. Of the patients, where the TB prescribed ET, 5 % (n = 31) decided against ET. This decision was associated with fear of ET (OR = 2.2; 95 % CI 1.0–5.2) and higher age (OR 9; 95 % CI 1.0–48.1). Psychiatric co-morbidity (OR = 1.8; 95 % CI 0.7–4.2), poor QoL (OR = 0.4; 95 % CI 0.2–1.2), and education (OR = 1.2; 95 % CI 0.5–2.6) were not associated with the decision.

Discussion

Guideline adherent implementation of adjuvant ET is high. Physicians’ decision against ET is mainly associated with patients’ younger age and poor quality of life, whereas patients’ decision, once the TB decided to initiate ET and if ET is indicated by guidelines, is associated with higher age and fear of ET.

     

Cardiac late effects after modern 3D-conformal radiotherapy in breast cancer patients: a retrospective cohort study in Germany (ESCaRa)

Breast Cancer Research and Treatment - Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques...     

The risk of urinary incontinence after partial urethral resection in patients with anterior vulvar cancer

Objective

The number of women with vulvar carcinoma located in the anterior fourchette in immediate proximity to the urethral opening has increased. A retrospective analysis was performed in order to evaluate the risk of urinary incontinence after tumor-resection, standard inguinal lymphadenectomy and additional partial urethral resection.

Study design

Between 2002 and 2007, 19 women with vulvar carcinomas located close to the urethral opening and consequently treated by additional partial urethral resection of up to 1.5 cm, were evaluated for urinary loss postoperatively by standard incontinence questionnaire. All patients complaining about some kind of urinary loss underwent urodynamic measurement. Results were compared with 21 controls (women with anterior vulvar cancer treated without urethral resection).

Results

Five of 19 women (26%) of the study group complained about urinary disturbances and received urodynamic evaluation. Ninety-five percent of the patients (18/19 women) were continent by urodynamic criteria; in one woman the measurement was unreliable. One patient in the control group (1/21 women) complained of an increase of urge symptoms that had been present preoperatively.

Conclusions

Twenty-six percent of our patients after partial urethral resection reported incontinence symptoms, though this was not always confirmed by urodynamics. We conclude that the risk of urinary stress incontinence after partial urethral resection in anterior vulvar carcinoma is acceptable.     

A randomized, double-blind, placebo-controlled, phase 3 trial comparing SMS 201-995 pa LAR plus tamoxifen versus tamoxifen plus placebo in women with locally recurrent or metastatic breast cancer]

A randomized, double-blind, placebo-controlled, phase 3 trial comparing SMS 201-995 pa LAR plus tamoxifen versus tamoxifen plus placebo in women with locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: Numerous studies have proved the efficacy of tamoxifen treatment in women with receptor-positive breast cancer. Preclinical and phase I/II-studies showed that tumor control can be improved if Octreotid is added. In this randomized controlled double blind phase III study women received 20 mg tamoxifen daily and either 160 mg Octreoid-Depot i. m. injection once a month or a placebo injection. Until 1998 a total of 263 women were randomized. RESULTS: The study medication was tolerated well by all patients in the treatment group (n = 133). The most frequent moderate side effects were diarrhea (n = 73), nausea (n = 26), abdominal pain (n = 19), bone pain (n = 24) and fatigue (n = 20). No patient dropped out because of these side effects. Surprisingly, several complete remissions occured. Neither the total survival nor the progression free survival was significantly different between groups. Therefore the study was stopped before the originally planned number of patients (n = 416) had been enrolled. CONCLUSION: Octreotid plus tamoxifen does not improve tumor control. It is necessary to define subgroups that might benefit from Octreotid.     

Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy.

PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important. PATIENTS AND METHODS: According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients' prognosis. RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P =.032 and P =.014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P =.031) in our series. CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.     

The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C

Background Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy.Methods Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models.Results AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89–1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80–1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86–1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77–1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3–4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology.Conclusion For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.Subject terms: Randomized controlled trials, Breast cancer     

Prognostic impact of circulating tumor cells assessed with the CellSearch System? and AdnaTest Breast? in metastatic breast cancer patients: the DETECT study

Introduction

There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies.

Methods

In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions.

Results

With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p<0.001). This prognostic impact for OS was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p = 0.197). In multivariate analysis, the presence of CTCs was an independent predictor for OS (HR: 2.7, 95%-CI: 1.6-4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS.

Conclusions

The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch system is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer.

Trial registration

Current Controlled Trials Registry number ISRCTN59722891.     

Novel Method for Three-Dimensional Facial Expression Recognition Using Self-Normalizing Neural Networks and Mobile Devices

Introduction To date, most ways to perform facial expression recognition rely on two-dimensional images, advanced approaches with three-dimensional data exist. These however demand stationary apparatuses and thus lack portability and possibilities to scale deployment. As human emotions, intent and even diseases may condense in distinct facial expressions or changes therein, the need for a portable yet capable solution is signified. Due to the superior informative value of three-dimensional data on facial morphology and because certain syndromes find expression in specific facial dysmorphisms, a solution should allow portable acquisition of true three-dimensional facial scans in real time. In this study we present a novel solution for the three-dimensional acquisition of facial geometry data and the recognition of facial expressions from it. The new technology presented here only requires the use of a smartphone or tablet with an integrated TrueDepth camera and enables real-time acquisition of the geometry and its categorization into distinct facial expressions. Material and Methods Our approach consisted of two parts: First, training data was acquired by asking a collective of 226 medical students to adopt defined facial expressions while their current facial morphology was captured by our specially developed app running on iPads, placed in front of the students. In total, the list of the facial expressions to be shown by the participants consisted of “disappointed”, “stressed”, “happy”, “sad” and “surprised”. Second, the data were used to train a self-normalizing neural network. A set of all factors describing the current facial expression at a time is referred to as “snapshot”. Results In total, over half a million snapshots were recorded in the study. Ultimately, the network achieved an overall accuracy of 80.54% after 400 epochs of training. In test, an overall accuracy of 81.15% was determined. Recall values differed by the category of a snapshot and ranged from 74.79% for “stressed” to 87.61% for “happy”. Precision showed similar results, whereas “sad” achieved the lowest value at 77.48% and “surprised” the highest at 86.87%. Conclusions With the present work it can be demonstrated that respectable results can be achieved even when using data sets with some challenges. Through various measures, already incorporated into an optimized version of our app, it is to be expected that the training results can be significantly improved and made more precise in the future. Currently a follow-up study with the new version of our app that encompasses the suggested alterations and adaptions, is being conducted. We aim to build a large and open database of facial scans not only for facial expression recognition but to perform disease recognition and to monitor diseases’ treatment progresses.