The effect of self-management techniques on relevant outcomes in chronic low back pain: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Among many treatment approaches for chronic low back pain (CLBP), self-management techniques are becoming increasingly important. The aim of this paper was to (a) provide an overview of existing digital self-help interventions for CLBP and (b) examine the effect of these interventions in reducing pain intensity, pain catastrophizing and pain disability. DATABASES AND DATA TREATMENT: Following the PRISMA guideline, a systematic literature search was conducted in the MEDLINE, EMBASE, PsychInfo, CINAHL and Cochrane databases. We included randomized controlled trials from the last 10 years that examined the impact of digital self-management interventions on at least one of the three outcomes in adult patients with CLBP (duration ≥3 months). The meta-analysis was based on random-effects models. Standardized tools were used to assess the risk of bias (RoB) for each study and the quality of evidence for each outcome. RESULTS: We included 12 studies (n = 1545). A small but robust and statistically significant pooled effect was found on pain intensity (g = 0.24; 95% CI [0.09, 0.40], k = 12) and pain disability (g = 0.43; 95% CI [0.27, 0.59], k = 11). The effect on pain catastrophizing was not significant (g = 0.38; 95% CI [-0.31, 1.06], k = 4). The overall effect size including all three outcomes was g = 0.33 (95% CI [0.21, 0.44], k = 27). The RoB of the included studies was mixed. The quality of evidence was moderate or high. CONCLUSION: In summary, we were able to substantiate recent evidence that digital self-management interventions are effective in the treatment of CLBP. Given the heterogeneity of interventions, further research should aim to investigate which patients benefit most from which approach. SIGNIFICANCE: This meta-analysis examines the effect of digital self-management techniques in patients with CLBP. The results add to the evidence that digital interventions can help patients reduce their pain intensity and disability. A minority of studies point towards the possibility that digital interventions can reduce pain catastrophizing. Future research should further explore which patients benefit most from these kinds of interventions.

Mast cell-deficient mice Mcpt5Cre/Dicer fl/fl redefine the role of mast cells in experimental bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease of the skin affecting the elderly. BP is immunopathologically characterized by autoantibodies against BP180 and BP230. With the growing evidence of cell-mediated autoimmunity in the pathogenesis of BP, it still remains unclear whether mast cells (MCs) are involved, due to conflicting data obtained from Kit-dependent MC-deficient mouse models. Objectives: To clarify the role of MCs in experimental BP; the dynamics in cutaneous MC numbers, associated immune cells and the development of disease in Kit-independent MC-deficient mouse model. Methods: Employing a recently established murine adult passive transfer model of BP induced by the transfer of pathogenic immunoglobulin G (IgG), lesional skin biopsies were investigated histologically and immunohistochemically for the time-dependent MC accumulation and dermal infiltration. Results: The numbers of cutaneous MCs increased following the induction of BP, in part, maintained by MC proliferation. Numbers of T cells, neutrophils and eosinophils in the skin also increased after BP induction, with eosinophils showing a preferential co-localization with MCs. Furthermore, clinical disease manifestation in MC-deficient Mcpt5Cre/Dicer fl/fl mice remained unchanged compared to MC-sufficient Dicer fl/fl mice. The composition of the immune cell infiltration including as T cells, neutrophils and eosinophils was largely unaffected by the absence of MCs. Conclusion: MCs do not play a pivotal role in the pathogenesis of passive IgG-transfer mediated BP model. Their increase in number may be a bystander effect following tissue injury. We therefore suggest caution regarding the selection of MCs as sole targets for the development of novel drugs for BP.

A Comprehensive Multi-Analyte Method for Hair Analysis: Substance-Specific Quantification Ranges and Tool for Task-Oriented Data Evaluation.

The aim of the present study was to quantify a large number of analytes including opioids, stimulants, benzodiazepines, z-drugs, antidepressants and neuroleptics within a single sample workup followed by a single analytical measurement. Expected drug concentrations in hair are strongly substance dependent. Therefore, three different calibration ranges were implemented: 0.5 to 600 pg/mg (group 1), 10 to 12,000 pg/mg (group 2) and 50 to 60,000 pg/mg (group 3). In order to avoid saturation effects, different strategies were applied for selected transitions including the use of parent mass ions containing one or two 13C-isotopes and detuning of the declustering potential and/or collision energy. Drugs were extracted from pulverized hair by a two-step extraction protocol and measured by liquid chromatrography--tandem mass spectrometry (LC--MS-MS) using Scheduled MRM™ Algorithm Pro. In total, 275 MRM transitions including 43 deuterated standards were measured. The method has been fully validated according to international guidelines. A MultiQuant™ software based tool for task-oriented data evaluation was established, which allows extracting selected information from the measured data sets. The matrix effects and recoveries were within the allowed ranges for the majority of the analytes. The lower limits of quantification (LLOQs) were for ∼72% of the analytes in the low-pg/mg range (0.5-5 pg/mg) and for ∼24% of the analytes between 10 and 50 pg/mg. These LLOQs considered cut-offs by the Society of Hair Testing (SoHT), if recommended. The herein established multi-analyte approach meets the specific requirements of forensic hair testing and can be used for the rapid and robust measurement of a wide range of psychoactive substances. The analyte-specific wide concentration ranges open up a wide field of applications.

Health news sharing is reflected in distributed reward-related brain activity.

Neuroimaging has identified individual brain regions, but not yet whole-brain patterns, that correlate with the population impact of health messaging. We used neuroimaging to measure whole-brain responses to health news articles across two studies. Beyond activity in core reward value-related regions (ventral striatum, ventromedial prefrontal cortex), our approach leveraged whole-brain responses to each article, quantifying expression of a distributed pattern meta-analytically associated with reward valuation. The results indicated that expression of this whole-brain pattern was associated with population-level sharing of these articles beyond previously identified brain regions and self-report variables. Further, the efficacy of the meta-analytic pattern was not reducible to patterns within core reward value-related regions but rather depended on larger-scale patterns. Overall, this work shows that a reward-related pattern of whole-brain activity is related to health information sharing, advancing neuroscience models of the mechanisms underlying the spread of health information through a population.

Prognostic factors for and pattern of lymph-node involvement in patients with operable cervical cancer.

PURPOSE: Lymph node metastases significantly worsen the prognosis in cervical carcinoma. Risk factors-pathological and patient related-could select patients at high risk for lymph node involvement. METHODS: This retrospective analysis was performed by analyzing data from patients with cervical carcinoma treated between 2000 and 2017 at the Department of Obstetrics and Gynecology of the University Hospital Ulm. RESULTS: In total, 261 patients with cervical carcinoma (International Federation of Gynecology and Obstetrics (FIGO) stage IA-IIB) and lymphadenectomy with at least 10 removed lymph nodes were available for analysis. Overall, 86 (33.0%) patients had lymph node metastases; 73 patients had pelvic lymph node metastases only and 13 patients had both pelvic and paraaortic lymph node metastases. Lymph node metastases were found most often in the region of the external iliac artery and obturator fossa, with 57.0% and 54.7% of all 86 node-positive patients, respectively. Univariable analyses showed that presence of lymph node metastases was significantly associated with both preoperative FIGO stage (p = 0.001) and final pathological tumor stage (p < 0.001), status of resection margin (p = 0.002), lymphovascular space invasion (LVSI), (p < 0.001) and vascular space invasion, (p < 0.001). In a multivariable logistic regression model with presence of lymph node metastases (yes/no) as binary response variable, only LVSI (p < 0.001) and body mass index (BMI), (p = 0.035) remained as significant independent predictors of lymph node involvement. Subgroup analyses showed that LVSI was a significant predictive factor for lymph node involvement in patients with a preoperatively assessed FIGO stage < IIB (p < 0.001), but not for patients with a preoperatively assessed FIGO stage ≥ IIB (p = 0.122). CONCLUSIONS: The risk factor LVSI should play an important role in deciding whether an individualized therapy concept is based on escalating or deescalating treatment. In future, the sentinel concept could reduce morbidity and at the same time provide an important prognostic assessment for a subset of cervical cancer patients.

Cognitive regulation of ventromedial prefrontal activity evokes lasting change in the perceived self-relevance of persuasive messaging.

Persuasive messages can change people's thoughts, feelings, and actions, but these effects depend on how people think about and appraise the meaning of these messages. Drawing from research on the cognitive control of emotion, we used neuroimaging to investigate neural mechanisms underlying cognitive regulation of the affective and persuasive impact of advertisements communicating the risks of binge drinking, a significant public health problem. Using cognitive control to up-regulate (vs. down-regulate) responses to the ads increased: negative affect related to consequences of excessive drinking, perceived ad effectiveness, and ratings of ad self-relevance made after a one-hour delay. Neurally, these effects of cognitive control were mediated by goal-congruent modulation of ventromedial prefrontal cortex and distributed brain patterns associated with negative emotion and subjective valuation. These findings suggest that people can leverage cognitive control resources to deliberately shape responses to persuasive appeals, and identify mechanisms of emotional reactivity and integrative valuation that underlie this ability. Specifically, brain valuation pattern expression mediated the effect of cognitive goals on perceived message self-relevance, suggesting a role for the brain's valuation system in shaping responses to persuasive appeals in a manner that persists over time.

Brain Activity Tracks Population Information Sharing by Capturing Consensus Judgments of Value.

Information that is shared widely can profoundly shape society. Evidence from neuroimaging suggests that activity in the ventromedial prefrontal cortex (vmPFC), a core region of the brain's valuation system tracks with this sharing. However, the mechanisms linking vmPFC responses in individuals to population behavior are still unclear. We used a multilevel brain-as-predictor approach to address this gap, finding that individual differences in how closely vmPFC activity corresponded with population news article sharing related to how closely its activity tracked with social consensus about article value. Moreover, how closely vmPFC activity corresponded with population behavior was linked to daily life news experience: frequent news readers tended to show high vmPFC across all articles, whereas infrequent readers showed high vmPFC only to articles that were more broadly valued and heavily shared. Using functional connectivity analyses, we found that superior tracking of consensus value was related to decreased connectivity of vmPFC with a dorsolateral PFC region associated with controlled processing. Taken together, our results demonstrate variability in the brain's capacity to track crowd wisdom about information value, and suggest (lower levels of) stimulus experience and vmPFC-dlPFC connectivity as psychological and neural sources of this variability.

Clinical implications of fracture-associated vascular damage in extremity and pelvic trauma.

BACKGROUND: Vascular damage in polytrauma patients is associated with high mortality and morbidity. Therefore, specific clinical implications of vascular damage with fractures in major trauma patients are reassessed. METHODS: This comprehensive nine-year retrospective single center cohort study analyzed demography, laboratory, treatment and outcome data from 3689 patients, 64 patients with fracture-associated vascular injuries were identified and were compared to a control group. RESULTS: Vascular damage occurred in 7% of patients with upper and lower limb and pelvic fractures admitted to the trauma room. Overall survival was 80% in pelvic fracture and 97% in extremity fracture patients and comparable to non-vascular trauma patients. Additional arterial damage required substantial fluid administration and was visible as significantly anemia and disturbed coagulation tests upon admission. Open procedures were done in over 80% of peripheral extremity vascular damage. Endovascular procedures were predominant (87%) in pelvic injury. CONCLUSION: Vascular damage is associated with high mortality rates especially in combination with pelvic fractures. Initial anemia, disturbed coagulation tests and the need for extensive pre-clinical fluid substitution were observed in the cohort with vascular damage. Therefore, fast diagnosis and early interventional and surgical procedures are necessary to optimize patient-specific outcome.

Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma.

Ataxia-oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive neurologic disorder. The phenotype is characterized by ataxia, oculomotor apraxia, peripheral neuropathy and dystonia. AOA4 is caused by biallelic pathogenic variants in the PNKP gene encoding a polynucleotide kinase 3'-phosphatase with an important function in DNA-damage repair. By whole exome sequencing, we identified 2 variants within the PNKP gene in a 27-year-old German woman with a clinical AOA phenotype combined with a cerebellar pilocytic astrocytoma diagnosed at 23 years of age. One variant, a duplication in exon 14 resulting in the frameshift c.1253_1269dup p.(Thr424fs*49), has previously been described as pathogenic, for example, in cases of AOA4. The second variant, representing a nonsense mutation in exon 17, c.1545C>G p.(Tyr515*), has not yet been described and is predicted to cause a loss of the 7 C-terminal amino acids. This is the first description of AOA4 in a patient with central European descent. Furthermore, the occurrence of a pilocytic astrocytoma has not been described before in an AOA4 patient. Our data demonstrate compound heterozygous PNKP germline variants in a German patient with AOA4 and provide evidence for a possible link with tumor predisposition. Localization of the 2 variants in human PNKP NP_009185.2. NM_007254.3:c.1253_1269dup p.(Thr424fs*49) is predicted to cause a frameshift within the kinase domain, NM_007254.3:c.1545C>G p.(Tyr515*) is predicted to cause loss of 2 C-terminal amino acids of the kinase domain and 5 additional C-terminal amino acids.

Adverse events of group psychotherapy in the in-patient setting - results of a naturalistic trial.

OBJECTIVE: Adverse events of psychotherapy have often been neglected in research. In this study, potential adverse events of group psychotherapies in a psychiatric hospital were systematically assessed, explored for predictors and linked to treatment outcome. METHOD: A naturalistic trial was conducted in 180 in-patients attending different group psychotherapies. Adverse events were assessed using three different measures: (i) weekly reporting of unwanted treatment reactions, (ii) mood changes in response to every single group session and (iii) premature group termination. RESULTS: Different measures of adverse events were weakly associated. Deterioration of mood state and/or unwanted treatment reactions were experienced by 60-65% of all patients. Reports of unwanted treatment reactions decreased over time and were negatively associated with symptom improvement. However, mood state deterioration was constant and unrelated to treatment outcome. The rate of premature group termination was 34%. Significant predictors of adverse events included patient characteristics as well as disadvantageous group conditions. CONCLUSIONS: For the majority of patients, group psychotherapy in the in-patient setting is associated with adverse events. Changes over time and a strong correlation with general symptom severity must be considered in the assessment and interpretation of adverse events. Predictors should be considered as potential risk factors in future research.

A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne patients and healthy controls.

BACKGROUND: Cutibacterium (Propionibacterium) acnes is assumed to play an important role in the pathogenesis of acne. OBJECTIVES: To examine if clones with distinct virulence properties are associated with acne. METHODS: Multiple C. acnes isolates from follicles and surface skin of patients with moderate to severe acne and healthy controls were characterized by multilocus sequence typing. To determine if CC18 isolates from acne patients differ from those of controls in the possession of virulence genes or lack of genes conducive to a harmonious coexistence the full genomes of dominating CC18 follicular clones from six patients and five controls were sequenced. RESULTS: Individuals carried one to ten clones simultaneously. The dominating C. acnes clones in follicles from acne patients were exclusively from the phylogenetic clade I-1a and all belonged to clonal complex CC18 with the exception of one patient dominated by the worldwide-disseminated and often antibiotic resistant clone ST3. The clonal composition of healthy follicles showed a more heterogeneous pattern with follicles dominated by clones representing the phylogenetic clades I-1a, I-1b, I-2 and II. Comparison of follicular CC18 gene contents, allelic versions of putative virulence genes and their promoter regions, and 54 variable-length intragenic and inter-genic homopolymeric tracts showed extensive conservation and no difference associated with the clinical origin of isolates. CONCLUSIONS: The study supports that C. acnes strains from clonal complex CC18 and the often antibiotic resistant clone ST3 are associated with acne and suggests that susceptibility of the host rather than differences within these clones may determine the clinical outcome of colonization.

Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS.

Direct therapeutic targeting of oncogenic RAS is currently still impossible due to lack of suitable pharmacological inhibitors. Because specific blockade of druggable RAS effectors might represent an alternative treatment approach, we evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was required to strongly induce apoptosis in human MM cell lines (HMCLs), in primary MM cells in vitro, and in a syngeneic MM mouse model in vivo. The anti-MM effect of pan-Raf inhibition did not correlate with the RAS mutation status, and functionally appeared to involve both MEK-dependent and -independent mechanisms. Furthermore, transcriptome analyses revealed that pan-Raf activity affects PI3K-dependent signalling, thus highlighting a functional link between the RAS/Raf and PI3K/mTOR/Akt pro-survival pathways. Accordingly, pharmacological inhibition of PI3K strongly enhanced the anti-MM effect of pan-Raf inhibition in MM cell lines and in primary MM cells in vitro and in vivo. Concomitant pan-Raf/PI3K inhibition was also effective in carfilzomib- and lenalidomide-resistant MM models underscoring that this attractive therapeutic anti-MM strategy is suitable for immediate clinical translation.

A progressively wetter climate in southern East Africa over the past 1.3 million years.

African climate is generally considered to have evolved towards progressively drier conditions over the past few million years, with increased variability as glacial-interglacial change intensified worldwide. Palaeoclimate records derived mainly from northern Africa exhibit a 100,000-year (eccentricity) cycle overprinted on a pronounced 20,000-year (precession) beat, driven by orbital forcing of summer insolation, global ice volume and long-lived atmospheric greenhouse gases. Here we present a 1.3-million-year-long climate history from the Lake Malawi basin (10°-14° S in eastern Africa), which displays strong 100,000-year (eccentricity) cycles of temperature and rainfall following the Mid-Pleistocene Transition around 900,000 years ago. Interglacial periods were relatively warm and moist, while ice ages were cool and dry. The Malawi record shows limited evidence for precessional variability, which we attribute to the opposing effects of austral summer insolation and the temporal/spatial pattern of sea surface temperature in the Indian Ocean. The temperature history of the Malawi basin, at least for the past 500,000 years, strongly resembles past changes in atmospheric carbon dioxide and terrigenous dust flux in the tropical Pacific Ocean, but not in global ice volume. Climate in this sector of eastern Africa (unlike northern Africa) evolved from a predominantly arid environment with high-frequency variability to generally wetter conditions with more prolonged wet and dry intervals.

Constructed wetlands may lower inorganic nutrient inputs but enhance DOC loadings into a drinking water reservoir in North Wales.

The objective of this study was to monitor a newly constructed wetland (CW) in north Wales, UK, to assess whether it contributes to an improvement in water quality (nutrient removal) of a nearby drinking water reservoir. Inflow and outflow of the Free Water Surface (FWS) CW were monitored on a weekly basis and over a period of 6 months. Physicochemical parameters including pH, conductivity and dissolved oxygen (DO) were measured, as well as nutrients and dissolved organic and inorganic carbon (DOC, DIC) concentration. The CW was seen to contribute to water quality improvement; results show that nutrient removal took place within weeks after construction. It was found that 72 % of initial nitrate (N03 (-)), 53 % of initial phosphate (PO4 (3-)) and 35 % of initial biological oxygen demand (BOD) were removed, calculated as a total over the whole sampling period. From our study, it can be concluded that while inorganic nutrients do decline in CWs, the DOC outputs increases. This may suggest that CWs represent a source for DOC. To assess the carbon in- and output a C budget was calculated.

[Influences on Placental Growth Factor (PlGF) and Soluble fms-like Tyrosine Kinase-1 (sFlt-1) Concentration Levels at the Time of First Trimester Screening]. / Einflussfaktoren auf die placental growth factor (PlGF) und soluble fms-like tyrosine kinase-1 (sFlt-1) Konzentration im Rahmen des Erst-Trimester-Screenings.

INTRODUCTION: The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are significantly altered in preeclampsia with elevated sFlt-1 levels and low PlGF in the continuation of pregnancies. Furthermore, patients with preeclampsia reveal significantly low PlGF levels in the first trimester. MATERIAL AND METHOD: We performed a retrospective study including 161 patients during the first trimester screening between 11+0 and 13+6 weeks of gestation. In addition, we analyzed sFlt-1 und PlGF in maternal serum with a Roche Elecsys(®) System. RESULTS: The mean values for sFlt-1 were 1 247,11±545,84 pg/ml and 47,00±22,62 pg/ml for PlGF. There is a positive correlation between sFlt-1 and PAPP-A MoM (rS=0,681, p<0,001), and PlGF and PAPP-A MoM (rS=0,465, p<0,001), respectively. There was a negative correlation between sFlt-1 and maternal body mass index (rS=-0,225, p=0,005). Overweight patients had significantly lower sFlt-1 values than patients with normal weight (p=0,003). PlGF and the crown-rump-length of the fetus showed a positive correlation (rS=0,27, p<0,001), whereas PlGF and the Pulsatility Index of the uterine arteries were negative correlated (rS=-0,235; p=0,012). Patients with a preexistent diabetes mellitus had significantly low sFlt-1 und PlGF (p<0,05) values. Smokers had significantly elevated PlGF-values (p<0,001). CONCLUSION: sFlt-1 and PlGF are influenced by various factors during the first trimester of pregnancy which can be relevant for correct interpretation. Further prospective studies may be necessary to validate our results. The aim should be to establish sFlt-1 and PlGF MoM values to allow for integration into a screening for preeclampsia in the first trimester.

Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC).

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common malignancy worldwide. The past decades have not led to substantial improvement in diagnosis and therapy. Analysis of miRNA-expression may help to determine the progression profiles and outcomes of many different diseases, including HNSCC. Therefore, in this investigation, 43 formalin-fixed, paraffin-embedded (FFPE) samples of oral squamous cell carcinoma were micro-dissected, analysed for expression of 30 miRNAs and were compared with non-tumorous tissue. Furthermore, correlation analysis was performed, investigating possible correlations of miRNA-expression and patient or tumour-linked data, such as age, sex, tumour stage and size. miRNA extraction from FFPE samples functioned well for OSCC, and several miRNAs were differently expressed in tumours compared with non-tumorous tissue (i.e., miR-99*; miR-224; miR-205*), indicating their possible utility as biomarkers. Moreover, some miRNAs showed significant correlations with clinical and pathological data (e.g. tumour size: miR-3156, P = 0.033; T-stage: miR-212, P = 0.0009).

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial.

Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.

Randomised phase III trial of FEC120 vs EC-docetaxel in patients with high-risk node-positive primary breast cancer: final survival analysis of the ADEBAR study.

BACKGROUND: Taxane-containing adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. This study compared efficacy and tolerability of epirubicin (E)/cyclophosphamide (C) followed by docetaxel (Doc) with a dose-dense 5-fluorouracil (F)+E+ C regimen. METHODS: The ADEBAR study was a randomised phase III trial for women with primary invasive breast cancer and ⩾4 metastatic axillary lymph nodes (n=1364). Treatment consisted of four 21-day cycles of E plus C, followed by four 21-day cycles of Doc (EC-Doc), or six 28-day cycles of E plus F plus C (FEC120). RESULTS: Disease-free survival (DFS) was similar in the two treatment arms as shown by multivariate Cox regression adjusted for other prognostic factors (EC-Doc vs FEC120, hazard ratio (HR): 1.087; 95% confidence interval (CI): 0.878-1.346, P=0.444). In addition, there was no significant difference in overall survival (OS) between the two groups (HR: 0.974; 95% CI: 0.750-1.264, P=0.841). Haematologic toxicity was more common in FEC120 recipients; non-haematologic toxicities occurred more frequently in the EC-Doc arm. The serious adverse event rate was significantly higher in the FEC120 group (29.7% vs 22.5%). CONCLUSIONS: EC-Doc provides a feasible and effective alternative therapy option to FEC120 with a different safety profile in this high-risk breast cancer cohort.