Hermelink K.,Ludwig Maximilians University of Munich |
Kuchenhoff H.,Ludwig Maximilians University of Munich |
Bauerfeind I.,Klinikum Landshut |
Lux M.P.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 4 more authors.
Psycho-Oncology | Year: 2010
Objective: Complaints of cognitive dysfunction are frequent among cancer patients. Many studies have identified neuropsychological compromise associated with cancer and cancer therapy; however, the neuropsychological compromise was not related to self-reported cognitive dysfunction. In this prospective study, the authors examined if confounding factors masked an underlying association of self-perceived cognitive function with actual cognitive performance. Determinants of self-perceived cognitive dysfunction were investigated. Methods: Self-perceived cognitive function and cognitive performance were assessed before treatment, at the end of treatment, and 1 year after baseline in 101 breast cancer patients randomized to standard versus intensified chemotherapy. Linear mixed-effects models were applied to test the relationships of performance on neuropsychological tests, patient characteristics, and treatment variables to self-reported cognitive function. Change of cognitive performance was tested as a predictor of change in self-reports. Results: Self-perceived cognitive function deteriorated during chemotherapy and had partially recovered 1 year after diagnosis. The personality trait negative affectivity, current depression, and chemotherapy regimen were consistently related to cognitive self-reports. No significant associations with performance in any of the 12 cognitive tests emerged. Change of cognitive performance was not reflected in self-reports of cognitive function. Conclusions: Neuropsychological compromise and self-perceived cognitive dysfunction are independent phenomena in cancer patients. Generally, cancer-associated neuropsychological compromise is not noticed by affected patients, but negative affectivity and treatment burden induce pessimistic self-appraisals of cognitive functioning regardless of the presence of neuropsychological compromise. Clinicians should consider this when determining adequate therapy for patients who complain of 'chemobrain'. Copyright © 2010 John Wiley & Sons, Ltd.
Di Gioia D.,Ludwig Maximilians University of Munich |
Heinemann V.,Ludwig Maximilians University of Munich |
Nagel D.,Ludwig Maximilians University of Munich |
Untch M.,Helios Klinikum |
And 4 more authors.
Tumor Biology | Year: 2011
The aim of this retrospective analysis is to determine the correlation between tumour marker kinetics (TMK) like carcinoembryonic antigen (CEA) and/or cancer antigen (CA) 15-3 and imaging concerning effectiveness of chemotherapy in metastatic breast cancer (MBC) patients. TMK (CEA, AxSYM, Abbott; CA15-3, Elecsys, Roche) were evaluated in MBC patients (n=77) at the beginning of chemotherapy (pre-treatment value=A), after 20-30 days (first intermediate value=B), after 40-60 days (second intermediate value=C) and at the time the effectiveness of chemotherapy was evaluated with imaging (D). Response to treatment was assessed by standard WHO criteria criteria. For the assessment of biochemical progression and response, four criteria based on TMK were established. The first criterion of progression required that there was an increase ?25% after 40-60 days (C) and the slope per day from B to C exceeds the slope from A to B. The second criterion of progression required that, at the time of staging, the value be ?25% of the pre-treatment value (A), and also, increasing values from C until staging (D) were required. The first criterion of response required that the second intermediate value (C) be decreased by ?25% compared to A (pre-treatment value) and C be lower than B (first intermediate value). The second criterion of response required that D be ?25% of B and D be lower than C. Fifty-four (70%) patients showed a correlation between TMK and imaging results during chemotherapy. In 10 (13%) patients, no correlation was obtained, and in 13 (17%) patients, no biochemical statement was possible because of divergent TMK. In summary, after 1 month, no statement about treatment response was possible by using TMK. The effectiveness or ineffectiveness of treatment could be determined correctly in 40% of patients after 2 months and in 70% of patients after approximately 3 months. The data presented support the hypothesis that TMK are clinically relevant tools to monitor treatment response. Further improvements on their sensitivity can be probably achieved by a prospective study design and by combining with other biomarkers like CA-125 and HER2 shed antigen. © International Society of Oncology and BioMarkers (ISOBM) 2011.
von Minckwitz G.,German Breast Group |
von Minckwitz G.,University Hospital |
Rezai M.,Breast Center |
Fasching P.A.,University Hospital |
And 15 more authors.
Annals of Oncology | Year: 2014
Background: The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracyclinetaxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses. Patients and methods: Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years. Results: Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low. Conclusions: Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates. Clinical trial number: NCT 00288002, www.clinicaltrials.gov. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
PubMed | SpheroTec GmbH, Hospital of the LMU Munich, Klinikum Harlaching, Ludwig Maximilians University of Munich and 2 more.
Type: Journal Article | Journal: Journal of translational medicine | Year: 2016
Targeted anti-HER2 therapy has greatly improved the prognosis for many breast cancer patients. However, treatment for HER2 negative disease is currently still selected from a multitude of untargeted chemotherapeutic treatment options. A predictive test was developed using patient-derived spheroids to identify the most effective therapy for patients with HER2 negative breast cancer of all stages, for clinically relevant subgroups, as well as individual patients.Tumor samples from 120 HER2 negative patients obtained through biopsy or surgical excision were tested in the breast cancer spheroid model using scaffold-free cell culture. Similarly, spheroids were also generated from established HER2 negative breast cancer cell lines T-47D, MCF7, HCC1143, and HCC1937 to compare treatment efficacy of heterogeneous cell populations from patient tumor tissue with homogeneous cell lines. Spheroids were treated in vitro with guideline-recommended compounds. Treatment mediated impact on cell survival was subsequently quantified using an ATP assay.Differences were observed in the metabolic activity of the untreated spheroids, whereby cell lines consistently achieved higher values compared to tissue spheroids (p<0.001). A higher number of cells per spheroid correlated with a higher basal metabolic activity in tissue-derived spheroids (p<0.01), while the opposite was observed for cell line spheroids (p<0.01). Recurrent tumors showed a higher mean vitality (p<0.01) compared to primary tumors. Except for taxanes, treatment efficacy for most tested compounds differed significantly between breast cancer tissue spheroids and breast cancer cell lines. Overall a high variability in treatment response in vitro was seen in the tissue spheroids regardless of the tested substances. A greater response to anthracycline/docetaxel was observed for hormone receptor negative samples (p<0.01). A higher response to 5-FU (p<0.01) and anthracycline (p<0.05) was seen in high grade tumors. Smaller tumor size and negative lymph node status were both associated with a higher treatment efficacy to anthracycline treatment combined with 5-FU (cT1/2 vs cT3/4, p=0.035, cN+vs cN-, p<0.05).The tissue spheroid model reflects current guideline treatment recommendations for HER2 negative breast cancer, whereas tested cell lines did not. This model represents a unique diagnostic method to select the most effective therapy out of several equivalent treatment options.
PubMed | University of Tübingen, Klinikum Essen Mitte, University of Hamburg, Breast Cancer Center and 11 more.
Type: | Journal: Breast (Edinburgh, Scotland) | Year: 2016
With the growing importance of neoadjuvant systemic therapy (NST) the assessment of post neoadjuvant axillary status is of increasing importance especially in patients who presented initially with suspicious nodes (cN1). This study aims to investigate the predictive value of palpation and axillary ultrasound of formerly cN1 patients following NST.The SENTINA trial (SENTinel NeoAdjuvant) is a 4-arm prospective multicenter study designed to evaluate the role of sentinel node biopsy (SLNB) in the context of neoadjuvant systemic treatment (NST) of breast cancer patients.1240 patients from 103 institutions entered the trial. 715 (arm C n=592; arm D n=123) patients, who presented initially cN1 underwent clinical evaluation of lymph node status following NST. Palpation alone demonstrated a sensitivity of 8.3%, specifity of 94.8% and a negative predictive value (NPV) of 46.6%. Ultrasound alone revealed a sensitivity of 23.9%, specificity 91.7%, and a NPV of 50.3%.The investigators combined classification (palpation and ultrasound) resulted in a sensitivity of 24.4%, specificity 91.4%, and a NPV of 50.3%. Investigators classified the axilla nodes as being unsuspicious (cN0) following NST in 592/715 patients; of them 298 (50.3%) were pN0, 151 (25.5%) had 1-2 histologically involved nodes and 143 (24.2%) had >2 histologically involved nodes.The diagnostic accuracy of ultrasound and palpation following NST is unacceptably low and additional tools for evaluation of the axillary lymph node status following NST are urgently needed.
Heckmann J.G.,Klinikum Landshut |
Dutsch M.,Sana Klinik Rummelsberg
European Journal of Neurology | Year: 2012
To present two patients with Miller Fisher syndrome (MFS) recurrence after 35 and 44years and review of the literature on recurring MFS. All identified cases with recurrent MFS were evaluated. Age, gender, clinical features of first and recurrent MFS, course of disease, laboratory findings, therapy and outcome were transformed into tables. Twenty-eight patients (16 men, 12 women; mean age at the first episode 34years (range 13-57years); mean age at the latest episode 47years (range 21-66years) with a total of 70 MFS episodes were identified. Twenty-one patients had a single recurrence, five patients had two recurrences, one patient had four recurrences and one patient had seven recurrences. The mean interval between attacks was 9.45years (3months to 44years). In 76% of the initial episodes and in 81% of the recurrent episodes, an infectious disease preceded MFS. Additional facial and bulbar symptoms and autonomic disturbances were frequent findings. Cerebrospinal fluid (CSF) and electrodiagnostic findings were unspecific. If tested, autoantibodies against GQ1b had been positive in all episodes. In about half of the patients, immunotherapy was applied. The outcome was favourable in most patients. Recurrence of MFS is a rare quite uniform condition with a mostly favourable prognosis. © 2011 The Author(s) European Journal of Neurology © 2011 EFNS.
Murawski N.,Medical School Hamburg |
Held G.,Medical School Hamburg |
Ziepert M.,University of Leipzig |
Kempf B.,Klinikum Landshut |
And 11 more authors.
Blood | Year: 2014
To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-E CFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patientswho did not ( P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with E CFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study. © 2014 by The American Society of Hematology.
Kuehn T.,The Interdisciplinary Center |
Bauerfeind I.,Klinikum Landshut |
Fehm T.,Heinrich Heine University Düsseldorf |
Fleige B.,Multidisciplinary Breast Center |
And 11 more authors.
The Lancet Oncology | Year: 2013
Background: The optimum timing of sentinel-lymph-node biopsy for breast cancer patients treated with neoadjuvant chemotherapy is uncertain. The SENTINA (SENTinel NeoAdjuvant) study was designed to evaluate a specific algorithm for timing of a standardised sentinel-lymph-node biopsy procedure in patients who undergo neoadjuvant chemotherapy. Methods: SENTINA is a four-arm, prospective, multicentre cohort study undertaken at 103 institutions in Germany and Austria. Women with breast cancer who were scheduled for neoadjuvant chemotherapy were enrolled into the study. Patients with clinically node-negative disease (cN0) underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arm A). If the sentinel node was positive (pN1), a second sentinel-lymph-node biopsy procedure was done after neoadjuvant chemotherapy (arm B). Women with clinically node-positive disease (cN+) received neoadjuvant chemotherapy. Those who converted to clinically node-negative disease after chemotherapy (ycN0; arm C) were treated with sentinel-lymph-node biopsy and axillary dissection. Only patients whose clinical nodal status remained positive (ycN1) underwent axillary dissection without sentinel-lymph-node biopsy (arm D). The primary endpoint was accuracy (false-negative rate) of sentinel-lymph-node biopsy after neoadjuvant chemotherapy for patients who converted from cN1 to ycN0 disease during neoadjuvant chemotherapy (arm C). Secondary endpoints included comparison of the detection rate of sentinel-lymph-node biopsy before and after neoadjuvant chemotherapy, and also the false-negative rate and detection rate of sentinel-lymph-node biopsy after removal of the sentinel lymph node. Analyses were done according to treatment received (per protocol). Findings: Of 1737 patients who received treatment, 1022 women underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arms A and B), with a detection rate of 99·1% (95% CI 98·3-99·6; 1013 of 1022). In patients who converted after neoadjuvant chemotherapy from cN+ to ycN0 (arm C), the detection rate was 80·1% (95% CI 76·6-83·2; 474 of 592) and false-negative rate was 14·2% (95% CI 9·9-19·4; 32 of 226). The false-negative rate was 24·3% (17 of 70) for women who had one node removed and 18·5% (10 of 54) for those who had two sentinel nodes removed (arm C). In patients who had a second sentinel-lymph-node biopsy procedure after neoadjuvant chemotherapy (arm B), the detection rate was 60·8% (95% CI 55·6-65·9; 219 of 360) and the false-negative rate was 51·6% (95% CI 38·7-64·2; 33 of 64). Interpretation: Sentinel-lymph-node biopsy is a reliable diagnostic method before neoadjuvant chemotherapy. After systemic treatment or early sentinel-lymph-node biopsy, the procedure has a lower detection rate and a higher false-negative rate compared with sentinel-lymph-node biopsy done before neoadjuvant chemotherapy. These limitations should be considered if biopsy is planned after neoadjuvant chemotherapy. Funding: Brustkrebs Deutschland, German Society for Senology, German Breast Group. © 2013 Elsevier Ltd.
PubMed | Klinikum Traunstein, Rotkreuzklinikum, Ludwig Maximilians University of Munich, Klinikum Dachau and 3 more.
Type: | Journal: Journal of cancer research and clinical oncology | Year: 2016
De novo stage IV breast cancer patients (BCBCBetween 1978 and 2013, 88,759 patients were diagnosed with 92,807 cases of invasive and non-invasive BC. Of these patients, 4756 patients had distant metastases (MET) at diagnosis. The 5-year survival rate improved from 17.4 to 24.7%, while the pattern of metastases did not change. Improved staging diagnostics, a screening programme and primary systemic therapy changed the composition of prognostic strata. Patients with a similar composition as the 1978-1987 cohort exhibited a median survival difference of 13months; however, neither univariate nor multivariate analysis showed a survival effect for the four periods as a surrogate indicator for changing treatments. HER2+ patients have with 27.6months a slightly longer survival than all other BCSurvival of de novo BC
PubMed | Otto Von Guericke University of Magdeburg and Klinikum Landshut
Type: Journal Article | Journal: Journal of neurological surgery. Part A, Central European neurosurgery | Year: 2015
The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign extensor response in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI).This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted values.There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p=0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p=0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1year was also highly significant (p0.016).The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most fundamental warning signs in the clinical monitoring of comatose patients.