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This paper investigates the aerodynamic impact of Gurney flaps on a research wind turbine of the Hermann-Föttinger Institute at the Technische Universität Berlin. The rotor radius is 1.5 meters and the blade configurations consist of the clean and the tripped baseline cases emulating the effects of forced leading edge transition. The wind tunnel experiments include three operation points based on tip speed ratios of 3.0, 4.3 and 5.6, reaching Reynold numbers of approximately 250,000. The measurements are taken by means of three different methods; Ultrasonic Anemometry in the wake, surface pressure taps in the mid-span blade region and strain gauges at the blade root. The retrofit application consists of two Gurney flap heights of 0.5 % and 1.0 % in relation to the chord length, which are implemented perpendicular to the pressure side at the trailing edge. As a result, the Gurney flap configurations evoke performance improvements in terms of the axial wake velocities, the angles-of-attack and the lift coefficients. The enhancement of the root bending moments imply an increase of both the rotor torque and the thrust. Furthermore, the aerodynamic impact appears to be more pronounced in the tripped case compared to the clean case. Gurney flaps are considered a worthwhile passive flow-control device in order to alleviate the adverse effects of early separation and leading edge erosion of horizontal axis wind turbines.

This experimental load control study presents results of an active trailing edge flap feedforward controller for wind turbine applications. The controller input is derived from pressure based lift estimation methods that rely either on a quasi-steady method, based on a three-hole probe, or on an unsteady method that is based on three selected surface pressure ports. Furthermore, a standard feedback controller, based on force balance measurements, is compared to the feedforward control. A Clark-Y airfoil is employed for the wing that is equipped with a trailing edge flap of x/c = 30 % chordwise extension. Inflow disturbances are created by a two-dimensional active grid. The Reynolds number is Re = 290,000 and reduced frequencies of k = 0.07 up to k = 0.32 are analyzed. Within the first part of the paper, the lift estimation methods are compared. The surface pressure based method shows generally more accurate results whereas the three-hole probe estimate overpredicts the lift amplitudes with increasing frequencies. Nonetheless, employing the latter as input to the feedforward controller is more promising as a beneficial phase lead is introduced by this method. A successful load alleviation was achieved up to reduced frequencies of k = 0.192.

Intrinsically conductive polyaniline possesses many desirable physical, chemical and biological properties. Combining those with the enhanced design flexibility, structural complexity and environmental sustainability of additive manufacturing opens up a whole new field for the design and development of various applications, from energy storage over printable electronics to conductive implants. However, additive manufacturing of polyaniline is still in the early stages and remains full of challenges and limitations to overcome. This paper gives a critical overview of this emerging field and the different 3D printing techniques for polyaniline and polyaniline-based composites, along with an outlook of areas with high potential for future research.

Recombinant protein therapeutics, vaccines, and plasma products have a long record of safety. However, the use of cell culture to produce recombinant proteins is still susceptible to contamination with viruses. These contaminations cost millions of dollars to recover from, can lead to patients not receiving therapies, and are very rare, which makes learning from past events difficult. A consortium of biotech companies, together with the Massachusetts Institute of Technology, has convened to collect data on these events. This industry-wide study provides insights into the most common viral contaminants, the source of those contaminants, the cell lines affected, corrective actions, as well as the impact of such events. These results have implications for the safe and effective production of not just current products, but also emerging cell and gene therapies which have shown much therapeutic promise.

Introduction: The aim of this nonrandomized study was to compare the ipsilateral breast tumor recurrence rates in patients with invasive breast cancer, who had been treated with breast conserving surgery and whole breast irradiation and conventional boost or intraoperative electron radiotherapy boost (IOERT). Patients and Methods: 378 patients were included in the study, 188 patients in group 1 (conventional boost) and 190 patients in group 2 (IOERT boost). Patients were comparable with regard to age, menopausal status, tumor size, histological type, grading and axillary lymph node status. Included were patients with invasive breast cancer pT1 and pT2, N0, N1, N2, M0, and breast conserving surgery with clear margins >3mm. Excluded were patients with DCIS only, patients with invasive breast cancers larger than pT2, patients after primary systemic therapy and patients with multicentric disease. All patients (group 1 and group 2) received postoperative whole breast irradiation of 51-56.1 Gy. Group 1 received postoperative electron boost irradiation of 12 Gy after whole breast irradiation and group 2 received one intraoperative electron boost of 9 Gy in a single fraction during surgery before whole breast irradiation. Results: The 10-years actuarial rates of ipsilateral breast tumor recurrence (IBTR), true local recurrence (TLR), distant recurrence (DR) and disease free survival (DFS) were 7.1% (95%CI, 3.2-11.0%), 4.8% (95%CI, 1.5-8.0%), 14,2% (95%CI, 9.1-19.4%) and 82.4% respectively in group1 and 2.7% (95%CI, 0.0-5.9%, P=0.062), 0.7% (95%CI, 0.0-2.0%, P=0.016), 13.6% (95%CI, 5.0-22.2%, P=0.90) and 84.0% (P= 0.76) respectively in group 2. Conclusion: Patients treated with IOERT boost and whole breast irradiation achieve excellent local control rates at 10 years and exhibit statistically significant decreased true local recurrence rates compared to patients treated with whole breast irradiation and conventional electron boost. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-06.

Fragestellung: Die OEGGG/AGO hat den Themenkomplex Fertilitat, Kontrazeption und Hormonersatz bei onkologischen Erkrankungen aktuell bearbeitet und stellt ein Konsensuspapiers vor. Fertilitat: Am starksten gonadotoxisch wirken Alkylanzien. Tamoxifen und Aromatasehemmer uben nur einen marginalen Einfluss auf die ovarielle Reserve aus. GnRH-Analoga schadigen Keimzellen nicht. Mit zunehmendem Lebensalter einer Frau nimmt die ovarielle Reserve und damit die Wahrscheinlichkeit, schwanger zu werden, kontinuierlich ab. Eine systemische Chemotherapie beschleunigt den physiologischen Vorgang der Reduktion von Primordialfollikeln unabhangig vom Lebensalter. Nach dem Abschluss einer Chemotherapie bzw. Antihormontherapie sollte zumindest 2 Monate abgewartet werden, um die Ovarialfunktion zu beurteilen. Dazu mussen auch biochemische Analysen herangezogen werden. Der zuverlassigste Parameter ist in dieser Hinsicht das Anti-Muller-Hormon (AMH; Muellerian Inhibiting Factor, MIF), da AMH wahrend des gesamten Zyklus einen stabilen Parameter darstellt. FSH- und Inhibin-B-Werte stellen lediglich Momentaufnahmen dar. Die Datenlage zur Medikation mit GnRH-Analoga parallel zur Chemotherapie zum Fertilitatserhalt ist derzeit noch nicht konklusiv. Die Methode der Ruhigstellung der Ovarien durch Ovulationshemmer hat sich v.a. bei hamatologischen Neoplasien wie dem Morbus Hodgkin als effektiv erwiesen. „Ovarian tissue banking“ und Methoden der assistierten Reproduktion sind als experimentell anzusehen und durfen nur in zertifizierten Zentren angeboten werden. Ahnliches gilt fur eine In-vitro-Fertilisierung vor der Chemotherapie („Emergency IVF“). Kontrazeption: Bei allen Malignomen mit Ausnahme des Mammakarzinoms konnen samtliche gangige Methoden der Kontrazeption eingesetzt werden. Beim Mammakarzinom wird generell die Anwendung eines Kupfer-Intrauterinpessars empfohlen. Tamoxifen ist kein Kontrazeptionsschutz. Werden aus onkologischer Sicht GnRH-Analoga verordnet, ist fur die Dauer der GnRH-Gabe keine zusatzliche Masnahme zur Kontrazeption notwendig. A working group of the OEGGG/AGO presents a consensus statement on fertility, contraception and hormone replacement therapy in oncologic patients. Fertility: Alkylating agents are the most gondadotoxic. Tamoxifen and aromatase inhibitors exert only a marginal influence on ovarian reserve. GnRH analogues do not damage germ cells. Increasing age is associated with reduced ovarian reserve and the probability of pregnancy. Systemic chemotherapy accelerates the physiological process of reduction of primordial follicles independently of age. Following cytotoxic or antihormonal treatment, ovarian function tests should not take place earlier than 2 months. Biochemical analyses should be included also. With regard to ovarian reserve, the most reliable parameter is the anti muellerian hormone (AMH; Muellerian Inhibiting factor, MIF) since its value remains stable throughout the cycle. This is not true for FSH and inhibin beta. Data on the medication with GnRH analogues in parallel to chemotherapy for fertility preservation are inconclusive. The method of ovulation inhibition via contraceptives has been shown effective mainly in hematologic diseases such as Hodgkin's disease. Ovarian tissue banking and methods of assisted reproduction can be considered experimental and thus may only be offered in certified centers. Similarly, in vitro fertilisation before chemotherapy (“emergency IVF”) is experimental. Contraception: The main methods of contraception can be used by all oncologic patients with the exception of breast cancer in which generally the placement of an intrauterine pessar is recommended. Tamoxifen is no contraceptive method. If, from the oncologic point of view, GnRH agonists are prescribed, no additional contraception is necessary.

Background A multicenter phase II study was conducted to analyze the clinical activity of the steroidal aromatase inhibitor exemestane in the neoadjuvant treatment of post-menopausal women with strongly ER- and/or PgR- positive operable breast cancer. Patients and methods From September 2000 to December 2003, 80 women were recruited for treatment with exemestane 25 mg once daily for 4 months. The primary end-point was the clinical response rate according the WHO criteria; the secondary end-points included toxicity and the number of patients who qualified for breast conserving surgery at the end of treatment, comparability of evaluation methods for response, potential alterations of hormone receptor and Her2/neu status during treatment. Results On an intention to evaluate analysis, according to the prespecified criteria the overall clinical objective response rate was 34%, the pCR rate was 3% and the rate of breast conserving surgery was 76%. When sonographic and mammographic longitudinal measurements were included in patients with missing palpation data, response rates were 38% and 41%, respectively. The tumor response was independent of the Her2/neu status which remained unchanged during treatment. In contrast, while the ER expression remained unaltered, downregulation of the PgR was observed. The treatment was well tolerated with no grade 3 and 4 toxicities except gastrointestinal (one grade 3 case) and hot flushes (two grade 3 cases). Conclusion This study shows that exemestane is effective and safe as a preoperative therapy in post-menopausal patients with strongly hormone receptor-positive breast cancer.

The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, −14.4% after 36 months; mean T score reduction, −1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, −17.3%; mean T score reduction, −2.6) compared with patients receiving tamoxifen/goserelin (BMD, −11.6%; mean T score reduction, −1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Monoclonal antibodies (Mab) are the fastest growing group of biopharmaceuticals in development. For production in mammalian cells, the four polypeptide chains of the immunoglobulin diheterotetramer must be assembled prior to exit from the endoplasmic reticulum. Various recombinant Mab expression vectors have been developed utilizing mono-and bicistronic expression cassettes encoded on one or two plasmids. However, there are only few studies providing information on the type of vector design optimal for stable or transient production of recombinant IgG. Consequently, in this study, we have constructed a series of mammalian expression vectors for the production of recombinant human or chimeric IgG antibodies with different expression cassette designs. Versions for monocistronic and bicistronic expression with different promoters and cistron arrangements were generated. Antibody production levels were evaluated in transiently transfected 293T and CHO-K1 cells. Furthermore, stable CHO cell lines were generated and analyzed for antibody production levels and stability. Our results indicate that compared to monocistronic expression, EMCV IRES-mediated bicistronic expression constructs yield similar antibody expression levels and show long-term stability in CHO cell lines. Addition of a third cistron encoding YFP was shown to facilitate screening and isolation of clones using a FACS sorter.

Die Exzision von Sentinel-Lymphknoten (LK) bekommt eine zunehmende Bedeutung bei der Diagnostik von Mundhohlen- und Oropharynxkarzinomen im Falle eines N0-Halses. Die Sentinel-Node-Biopsie (SNB) wurde in ihrer Wertigkeit als einzige chirurgische Staging-Masnahme untersucht. Im Rahmen eines multimodalen Behandlungskonzeptes wurde die SNB ohne elektive Neck-Dissection (ND) bei 70 Patienten im Rahmen der Operation des Primarius durchgefuhrt. Die Kontrolle der Genauigkeit erfolgte uber die Manifestation von Hals-LK-Metastasen bei 45 Patienten, die keine postoperative Bestrahlung erhalten hatten. Es konnten in 94% der Falle Sentinel-LK exzidiert werden; 9 Patienten (13%) hatten positive LK und erhielten eine therapeutische ND. Es kam zu 2 Hals-LK-Metastasen im Zusammenhang mit Zweitkarzinomen, alle anderen Patienten blieben regionar unauffallig (mediane Beobachtungszeit: 26 Monate). Die SNB konnte als Staging-Masnahme beim N0-Hals und T1- bis T3-Tumoren zu einer erheblichen Reduktion der Anzahl elektiver NDs fuhren. Sie kann gut in ein multimodales Behandlungsschema integriert werden.

Purpose Prerequisite for lymphoscintigraphy-guided sentinel lymph node (SLN) biopsy in head and neck cancer patients has been a previously untreated primary tumor to avoid disturbance of the lymphatic flow. We evaluated the feasibility in a multimodality treatment approach to oral and oropharyngeal cancer comprising presurgical intra-arterial chemotherapy of the primary tumor. Patients and methods In a prospective study of 35 consecutive patients with primary oral and anterior oropharyngeal cancer T1-4N0 treated with superselective intra-arterial chemotherapy with high-dose cisplatin, SLN scintigraphy was performed on the day of surgery, including gamma camera imaging before and hand-held gamma probe identification of the SLN during surgery. SLN biopsy was performed in 50 neck sides, followed by radical resection of the primary in the same session. Elective neck dissection was not carried out. The pattern of lymphatic drainage was recorded and compared with the literature on well-known patterns found in lymphographic studies and metastatic disease in neck dissection specimens of patients without presurgical treatment. Results Drainage patterns of SLN related to different primary locations mapped the mentioned comparison patterns. SLN drainage patterns gave strong evidence that there are SLN in levels 3 and 4 with direct drainage from the primary. After a median observation time of 24 months, no patients had a neck relapse. Conclusions The results suggest that intra-arterial chemotherapy of the primary tumor does not significantly alter lymphatic drainage and that SLN biopsy following intra-arterial chemotherapy is feasible and offers valid results comparable to those obtained from patients without presurgical treatment.

Objective: The diagnostic potential of F-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET) and technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (SPET) in early detection and differential diagnosis of early dementia was evaluated including a comparison of metabolic and perfusion indices (PI). Methods: Twenty-four patients with initial clinical suspicion of beginning dementia were examined, 12 of them with mild cognitive impairment. All patients underwent SPET and PET within 2 weeks. Data were compared with the final clinical diagnosis at follow-up – 9 with Alzheimer’s disease (AD), 1 with frontotemporal dementia, 1 with vascular dementia (VD), 7 with mixed type of dementia (MIX) and 6 without any type of dementia. Metabolic indices (MI) and PI were compared with each other. The regional cerebral blood flow difference (rCBFdiff) calculated as local uptake difference between the right and left hemisphere was measured for patients with VD and MIX. Results: PET showed higher sensitivity and specificity in identifying the different types of early dementia (44–91 and 78–89%, respectively) than SPET (11–64 and 79–89%, respectively), especially in detecting AD (sensitivity 44%, specificity 83%) and MIX (sensitivity 71%, specificity 78%). Especially in patients with mild cognitive impairment, PET was the superior imaging modality for predicting dementia. Using PET, dementia could be excluded in all patients who did not develop dementia during the follow-up. In all patients, a weak correlation between PI and MI was observed (rho = 0.64, p < 0.002). The rCBFdiff in patients with VD and MIX ranged from 7 to 37%. Conclusion: In this study on patients with initial suspicion of beginning dementia who underwent both imaging modalities, PET and SPET, PET was the superior imaging method, especially in the detection of early AD or MIX.

The human proteins MOCS1A and MOCS1B catalyze the conversion of a guanosine derivative to precursor Z during molybdenum cofactor biosynthesis. MOCS1A shares homology with S-adenosylmethionine (AdoMet)-dependent radical enzymes, which catalyze the formation of protein and/or substrate radicals by reductive cleavage of AdoMet through a [4Fe-4S] cluster. Sequence analysis of MOCS1A showed two highly conserved cysteine motifs, one near the N terminus and one near the C terminus. MOCS1A was heterologously expressed in Escherichia coli and purified under aerobic and anaerobic conditions. Individual mutations of the conserved cysteines to serine revealed that all are essential for synthesis of precursor Z in vivo. The type and properties of the iron-sulfur (FeS) clusters were investigated using a combination of UV-visible absorption, variable temperature magnetic circular dichroism, resonance Raman, Mössbauer, and EPR spectroscopies coupled with iron and acid-labile sulfide analyses. The results indicated that anaerobically purified MOCS1A is a monomeric protein containing two oxygen-sensitive FeS clusters, each coordinated by only three cysteine residues. A redox-active [4Fe-4S](2+,+) cluster is ligated by an N-terminal CX(3)CX(2)C motif as is the case with all other AdoMet-dependent radical enzymes investigated thus far. A C-terminal CX(2)CX(13)C motif that is unique to MOCS1A and its orthologs primarily ligates a [3Fe-4S](0) cluster. However, MOCS1A could be reconstituted in vitro under anaerobic conditions to yield a form containing two [4Fe-4S](2+) clusters. The N-terminal [4Fe-4S](2+) cluster was rapidly degraded by oxygen via a semistable [2Fe-2S](2+) cluster intermediate, and the C-terminal [4Fe-4S](2+) cluster was rapidly degraded by oxygen to yield a semistable [3Fe-4S](0) cluster intermediate.

To compare the new, 6th edition, UICC TNM staging system with the former edition, we updated TNM staging in patients with differentiated thyroid carcinoma.The new and old TNM classification systems for differentiated thyroid carcinoma were applied in a retrospective analysis of 169 patients who underwent therapy with radioiodine (131I) from 1975 through 2002 at the Department of Nuclear Medicine, Frankfurt.According to the new staging system, 83 patients (49%) were classified as T1 compared to 54 patients (32%) based on the former edition; 32 patients (19%) as T2 compared to 61 (36%) patients formerly. In 44 patients with minimal extrathyroid extension, formerly classified T4, the new TNM staging changed to T3, and no patient was classified T4. The one year relapse-free survival fraction under the former edition staging was 100% for T1 and 92.2% for T2, compared to 96.8% for new edition T1 and 93.3% for T2.The new TNM classification causes a significant change in staging. New T1 classified tumors had a slightly worse relapse-free survival fraction compared with the old T1 carcinomas. For patients treated at our department, the altered criteria for classifying extrathyroid extensions have had only a minor impact on disease management.

Scientifically, it has been well established that breast-conserving treatment (BCT) in patients with breast cancer does not impair overall prognosis as compared to mastectomy. Several randomized clinical trials in the past two decades have shown that survival rates in breast cancer are stage-dependent, but independent of the extent of surgical breast tissue removal, as long as the resection margins are free of tumor infiltration. The particular importance the breast shows for female psychology and social interaction and the potential for feelings of mutilation and impaired physical integrity are another argument for carefully considering the implications connected with ablative surgical procedures. As a rational and informed basis for the shift in paradigms of invasiveness, the scientific community has felt the need to evidence the concept that local procedures have no detrimental impact on survival in such patients. Proof has been elaborated repeatedly by many investigators from different areas of the world. 1–3 The extent of tissue removed in breast cancer surgery, however, can be a predictor for local failure rate. Local relapse following mastectomy depends on tumor stage, nodal stage, and the biologic aggressiveness of the tumor and usually is an indicator of poor prognosis. By contrast, local recurrence after BCT does not necessarily have an impact on survival. In any case, the psychological and subjective burden of local failure following such interventions must never be underestimated. Therefore, BCT in general calls for adjuvant radiotherapy, although it has been shown that in a highly selected group of patients at very low risk for locoregional relapse, radiotherapy may indeed not be required. 4 This issue is under investigation in a number of prospective clinical trials. By accepted academic standards, BCT combined with adjuvant radiotherapy should be regarded as the surgical treatment of choice in patients with stage I and II breast cancer, as stated by the Consensus Development Conference as early as 1990. 5 Yet in contrast to these well-established standards, for various reasons BCT has not been fully accepted in general practice. This unfortunate discrepancy is linked to specific factors with regard to both patients and physicians. BCT rates are at considerable variance between different countries, but also within highly industrialized nations. For example, differences are reported to be marked between states in the United States. 6,7 In addition to geographic factors, the treatment level of a given hospital department is a key issue for the degree to which BCT is accepted. Women treated at university or teaching hospitals had doubled chances to have their breast preserved, while women over 70 and patients from rural areas were less likely candidates for BCT. 8 The most important factor influencing a patient’s decision on the surgical procedure to be used has proven to be the treating physician’s recommendation, which is rarely questioned in routine practice. 9 Thus, surgeons play the key role in patients’ decision-making processes. Surgeons participating in clinical trials should be particularly well educated and trained at the highest level of medical knowledge. After all, one chief argument for performing clinical trials is that quality control is given considerable attention under such circumstances. This refers to primary trial endpoints as much as general medical care for patients, including quality control measurements applied to surgical techniques and the standards of histopathology. Since 1984, the Austrian Breast & Colorectal Cancer Study Group (ABCSG) has been conducting nationwide, multicenter clinical trials in patients with stage I and II breast cancer. This framework has provided the opportunity, over one and a half decades, to investigate BCT rates in women participating in these investigations throughout Austria. To minimize potential selection bias, we selected subjects with identical basic prognostic characteristics (tumor and nodal stage, receptor status, and age) for the present analysis.

Purpose: To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor–positive, early-stage breast cancer. Patients and Methods: A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years. Results: All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P = .89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P = .74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P = .0001). Conclusion: Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.

Summary: Purpose: Interictal [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60–90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity. Methods: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-m-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus. Results: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (rp 0.7, p 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found. Conclusions: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism. Key Words: Temporal lobe epilepsy—FDG-PET—Mitochondrial oxidative phosphorylation.

Einleitung: Seit der Einführung der Sentinellymphknotenbiopsie (SLNB) zum axillären Staging bei Mammakarzinompatientinnen hat sich diese Operationstechnik in den meisten Brustzentren etabliert. Die Idee, mit einem weniger invasiven Eingriff als der axillären Dissektion den Nodalstatus exakt zu evaluieren, ist faszinierend und entspricht dem Gesamtkonzept in der Behandlung des Mammakarzinoms, den operativen Eingriff so wenig invasiv wie möglich zu gestalten. An wenigen Abteilungen wurde bereits dazu übergegangen, bei negativem Sentinellymphknoten (SLN) auf die Axilladissektion zu verzichten. Patientinnen und Methode: Von März 1998 bis März 2002 wurde an unserer Abteilung an 500 Patientinnen mit invasivem Mammakarzinom die Technik der SLNB angewandt. Anfangs wurde die Axilladissektion direkt im Anschluss an die SLNB durchgeführt. Nach der Lernphase an 75 Patientinnen mit einer Sensitivität von 96,2% und einer falsch negativen Rate von 3,8%, wurde bei Patientinnen mit negativem SLN unter definierten Voraussetzungen auf eine Axilladissektion verzichtet. Zusätzlich wurde aber das Spektrum erweitert und die Methode bei Patientinnen mit multizentrischem Karzinom und bei Patientinnen nach neoadjuvanter Chemotherapie evaluiert. Zur Auffindung des SLN wurde die kombinierte Methode mit blauem Farbstoff und mit Technetium 99m markiertem Humanalbumin verwendet. Ergebnisse: 500 SLNB wurden durchgeführt. Die Detektionsrate für das gesamte Kollektiv betrug 86,2%. Nach Bereinigung der Patientinnen mit multizentrischem Karzinom und der Patientinnen nach neoadjuvanter Chemotherapie betrug die Detektionsrate 94,5%. Insgesamt war der SLN in 41,3% der Patientinnen positiv, in 58,7% der Patientinnen negativ. Diskussion: Die SLNB ist eine probate Alternative zur Axilladissektion bei Patientinnen mit Mammakarzinom unter definierten Voraussetzungen.

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P = .037 and P = .015), with a similar trend observed in OS (P = .195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.

We tested whether proteome reference maps established for one species can be used for cross-species protein identification by comparing two-dimensional protein gel patterns and protein identification data of two closely related bacterial strains and four plant species. First, proteome profiles of two strains of the fully sequenced bacterium Sinorhizobium meliloti were compared as an example of close relatedness, high reproducibility and sequence availability. Secondly, the proteome profiles of three legumes (Medicago truncatula, Melilotus alba and Trifolium subterraneum), and the nonlegume rice (Oryza sativa) were analysed to test cross-species similarities. In general, we found stronger similarities in gel patterns of the arrayed proteins between the two bacterial strains and between the plant species than could be expected from the sequence similarities. However, protein identity could not be concluded from their gel position, not even when comparing strains of the same species. Surprisingly, in the bacterial strains peptide mass fingerprinting was more reliable for species-specific protein identification than N-terminal sequencing. While peptide masses were found to be unreliable for cross-species protein identification, we present useful criteria to determine confident matching against species-specific expressed sequence tag databases. In conclusion, we present evidence that cautions the use of proteome reference maps and peptide mass fingerprinting for cross-species protein identification.

Eight patients (77 joints) with polyarthritis were treated systemically with 570 MBq (15.4 mCi) of rhenium 186 ((186)Re) hydroxyethylidenediphosphonate (HEDP). Pain and disease activity were assessed monthly. In six (75%) of eight patients, a single injection of (186)Re HEDP led to an improvement in disease activity. Systemic low-dose treatment with (186)Re HEDP can reduce pain and disease activity in patients with polyarthritis.

Intra-arterial iodine-131 labelled Lipiodol therapy for liver cancer has been investigated for safety and efficacy over a number of years, but data on radiation exposure of personnel have remained unavailable to date. The aim of this study was to assess the radiation exposure of the physician during intra-arterial 131I-Lipiodol therapy for liver malignancies and to develop appropriate radiation protection measures and equipment. During 20 intra-arterial administrations of 131I-Lipiodol (1110-1924 MBq), radiation dose equivalents (RDE) to the whole body, fingers and eyes of the physician were determined for (a) conventional manual administration through a shielded syringe, (b) administration with an automatic injector and (c) administration with a lead container developed in-house. Administration by syringe resulted in a finger RDE of 19.5 mSv, an eye RDE of 130-140 microSv, and a whole-body RDE of 108-119 microSv. The injector reduced the finger RDE to 5 mSv. With both technique (a) and technique (b), contamination of angiography materials was observed. The container allowed safe transport and administration of the radiopharmaceutical from 4 m distance and reduced the finger RDE to3 microSv and the eye RDE to1 microSv during injection. During femoral artery compression, radiation exposure to the fingers reached 170 microSv, but the whole-body dose could be reduced from a mean RDE of 114 microSv to 14 microSv. No more contamination occurred. In conclusion, radiation exposure was high when 131I-Lipiodol was administered by syringe or injector, but was significantly reduced with the lead container.

Summary Aim of this study was to determine whether the sentinel lymph nodes (SLNs) can be accurately identified in breast cancer patients with intradermal injection of the radiotracer above the primary tumour in comparison to peritumoural injection. Methods: In 45 women with breast cancer we performed lymphoscintigraphy on two separate days. We injected Tc-99m nanocolloid on the first day peritumourally, and on a separate day intradermally. The results of both investigations using different injection sites were compared in order to determine the number and location of SLNs. Results: The SLN identification rate using peritumoural injection was 71% (32 of 45 patients) and 96% (43 out of 45 patients) using intradermal injection. In 62% (28 of 45 patients) the number and location of the SLNs were identical. In 97% (31 of 32 patients) in whom a SLN was detected using peritumoural injection, the same SLNs reappeared with intradermal injection. There were no false negative findings with the peritumoural administration of tracer whereas the intradermal administration approach resulted in a false negative rate of 13%. Conclusion: In women with breast cancer the reproducibility of lymphoscintigraphy using peritumoural and intradermal injection sites was 62%. The intradermal injection modality enables the detection of a SLN in patients where the peritumoural injection failed but it has the disadvantage of a higher false negative rate in comparison to the peritumoural injection technique.

The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer’s disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P

Cet article fait etat de l'experience d'un centre TEP prive concernant plus de 4 500 patients examines, dont 70 % en oncologie, 20 % en neurologie et 8% en cardiologie. Les differentes prescriptions sont passees en revue, ainsi qu'un certain nombre d'aspects lies a l'organisation financiere (remboursements) et methodologiques (protocoles d'acquisition, approvisionnements en radiopharmaceutiques, preparation des patients et inconvenients).

Purpose : To assess the role of geographic misses in the interstitial boost treatment of breast cancer patients and to evaluate methods of optimizing breast implants in design, performance, and dosimetry. Methods and Materials : During lumpectomy, the tumor excision sites of 89 patients were marked by five hemoclips. Postoperative radiographs demonstrated the clips' positions with respect to the extension of the surgical cavity, which was demarcated by air and hematoseroma. Twenty-seven selected patients received interstitial boosts to the tumor bed. The implant was first designed according to the clinical assumptions of the tumor bed's topography and then compared with the radiological findings. Prior to brachytherapy, the planning of the implant's dimension and the needle guidance was performed under simulator control. Dose distributions were first calculated following the Paris System and then electively optimized for the target volume by changing source positions and dwell times. Results : Compared to clinical estimations, the radiological determination of the tumor bed's location revealed an overall potential of topographic errors of 51.8% (14 out of 27 patients), rising up to 78.5% in patients with large adipose breasts (11 out of 13 patients). This observation was due to a high mobility of the tissue, leading to varying tumor site projections at the time of mammography, surgery, and brachytherapy. In all patients, the presimulation of the implant resulted in an adequate coverage of the target volume. In 17 of the 27 treated patients, dose distributions were modified to achieve a higher dose delivery in zones where a higher residual tumor load was expected (boost-in-boost). Conclusion : Breast implants have a high potential of geographic misses that can be avoided by intraoperative clip demarcation. The delineation of the tumor bed allows for dose reports actually referring to the target volume and not to the implant system to be obtained. In addition, modern afterloading techniques offer possibilities of individual dose planning with regard to high risk subvolumes within the implanted tissue.

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with 99mTc-bicisate showed a "coupled" decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with 131I) and a negative FDG PET, in four cases 131I-negative lymph node metastases were detectable with PET. Even in the patients with concordant "staging", differences between 131I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of 131I-positive/FDG-negative, 131I-negative/FDG-positive and 131I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours 131I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.

Objective : The purpose of this study was to compare the binding of various typical and atypical neuroleptics to striatal D 2 dopamine receptors in schizophrenic patients. Method : Fifty-six inpatients with schizophrenia, including 14 with schizoaffective disorder and one with schizophreniform disorder, were evaluated. Fourteen patients were neuroleptic free. Single photon emission computed tomography (SPECT) was performed 90 minutes after intravenous injection of [ 123 I]benzamide ([ 123 I]IBZM). Subsequent semiquantitative analysis of D 2 receptor binding was done with the use of the basal ganglia (striatum)/frontal cortex (BG/FC) ratio of activity. Clinical symptoms were rated with the Positive and Negative Syndrome Scale and the Hamilton Depression Rating Scale. Results : The BG/FC ratios in patients taking typical neuroleptics were significantly lower than those in the neuroleptic-free subjects but not lower than those in the patients taking atypical neuroleptics (clozapine, remoxipride). For atypical antipsychotics, a dose-dependent relationship with striatal D 2 receptor binding could not be demonstrated. BG/FC ratios were not significantly correlated with clinical symptoms or with duration of illness. Conclusions : The results indicate that [ 123 I]IBZM SPECT is useful for semiquantitative imaging of striatal D 2 dopamine receptors and for estimating their blockade by neuroleptics. Thus, it may improve drug monitoring in psychiatric patients. Furthermore, the findings suggest a complex relationship between the antipsychotic effect of atypical neuroleptics and D 2 receptor blockade.

Purpose: Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy. Material and methods: Until 10/2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10 Gy was applied (90% reference isodose), preceding WBI with 50– 54 Gy (single doses 1.7–2 Gy). Results: At a median follow up of 72.4 months (0.8–239), only 16 in-breast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5–151 months after primary treatment. In multivariate analysis only grade 3 reached significance (p = 0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients

Aims: To evaluate the rate of axillary recurrences in sentinel lymph node (SLN) negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Methods: Between May 1999 and February 2001 all patients who had primary invasive breast cancer and were SLN negative were eligible for this prospective study. SLNB was performed by using the combined method with radioactive tracer and blue dye. SLNs were examined by frozen section, standard H/E staining and immunohistochemistry staining. SLN negative patients did not receive further ALND. Follow-up was done three-monthly with clinical controls, blood samples and ultrasound of the breast and axilla. An annual mammogram was performed. Results: 116 patients with T1 or T2 invasive breast cancer were included in this trial. All 116 patients had negative SLNs in frozen sections, in H/E staining and in immunohistochemistry staining. The mean number of removed SLNs was 2.03±1.22. Mean tumor size was 17.15±7.62 mm. Postmenopausal patients totalled 79.3 and 20.7% of patients were premenopausal. No local or axillary recurrences occurred at a mean duration of follow-up of 22.12±6.38 months. Conclusion: The absence of axillary recurrences after SLNB without ALND in SLN negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity. Short term results are very promising. SLNB without ALND in SLN negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumors.

Background: Malignant transformation of thyroid tissue in struma ovarii and metastasis are uncommon. Benign thyroid tissue may spread to the peritoneal cavity in rare cases, and pathologic examination of the peritoneal implants shows multiple nodules of varying sizes of mature thyroid tissue similar to struma ovarii. This condition is termed “peritoneal strumosis”. It is very rare and therefore, both the criteria for diagnosis and its management are under discussion. The recommended treatment of metastatic struma ovarii should contain, in addition to local resection of the extraovarian tumor, total thyroidectomy in conjunction with radioiodine scanning and radioiodine ablation. Case report: A 38 year-old woman had presented with benign struma ovarii 12 years previously. She was referred to our department because of a right ovarian tumor. After confirming the diagnoses of metastatic recurrent benign struma ovarii, we performed debulking surgery with the aim of resecting all tumor masses. The uterus, left adnexa, and pelvic peritoneum were surgically extracted “en bloc”. No macroscopic tumor was left post-operatively. The first post operative 123 I scintography with15 MBq iodine-123 one month post-operatively showed a small but suspicious focus in the front left perivesical pelvic area. In the ventral visual presentation multiple discrete foci, located in right perivesical, supravesical and in the ventral upper abdomen, were seen. We then referred the patient for thyroidectomy and radioiodine ablation. The following periodic follow-ups of the patient did not show any signs of recurrence or progression of the disease. Conclusion: Patient with benign metastatic struma ovarii (also known as Highly differentiated follicular carcinoma of ovarian origin - HDFCO) may affectively be treated with local resection of the extraovarian tumor and subsequent thyroidectomy followed by radioactive iodine ablation.

BACKGROUND During the last two decades, hydroxyapatite has become popular as alloplastic material for bone replacement in orthopedic and dental surgery. We investigated prospectively the feasibility of hydroxyapatite spheres as replacement of enucleated eyes. PATIENTS AND METHODS Thirty-three consecutive patients entered a prospective study designed to evaluate the results obtained after either primary (n = 26) or secondary (n = 7) implantation of a hydroxyapatite sphere as replacement of the enucleated eyeball. Each patient was examined preoperatively, 1, 2, and 4 months after surgery, as well as every 6 months thereafter. At each examination time the motility of both coralline sphere and overlying cosmetic prosthesis was evaluated and the conjunctival sac was carefully examined at the slit-lamp. RESULTS The postoperative follow-up averaged 10.5 months for the primary implantations and 7.2 months for the secondary implantations. Two implants had to be removed because of infection unresponsive to antibiotic treatment. Defects in the conjunctiva overlying the implant necessitated wound revision in two cases. A buccal mucosal graft was performed in two additional ones. A temporary cosmetic prosthesis could be fitted in all but two of the remaining patients as early as 3 weeks after surgery. Motility of at least 3 mm in all directions could be obtained in 31 cases. CONCLUSION Our study demonstrated that satisfactory motility and good biocompatibility can be achieved, at least in the medium term, with implantation of coralline hydroxyapatite spheres.

Summary Background Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid. Methods ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I–II) breast cancer receiving goserelin (3·6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing. Findings At a median follow-up of 62 months (range 0–114·4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0·68, 95% CI 0·51–0·91; p=0·009), although the difference was not significant in the tamoxifen (HR 0·67, 95% CI 0·44–1·03; p=0·067) and anastrozole arms (HR 0·68, 95% CI 0·45–1·02; p=0·061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0·67, 95% CI 0·41–1·07; p=0·09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1·08, 95% CI 0·81–1·44; p=0·591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1·75, 95% CI 1·08–2·83; p=0·02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121). Interpretation Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer. Funding AstraZeneca; Novartis.

ZusammenfassungDie striatale Dopamin-D2-Rezeptoranreicherung von 123J-IBZM wurde bei 32 Patienten (18 ohne und 14 mit neuroleptischer Therapie) semiquantitativ unter Anwendung verschiedener ROI-Techniken ausgewertet. Ziel der Studie war es, die von verschiedenen Untersuchern gefundenen unterschiedlichen Quotienten (Striatum/Kortex) unter dem Aspekt der angewandten ROI-Technik zu untersuchen. Es konnte gezeigt werden, daß bei Verwendung des gleichen SPECT-Systems keine größeren Unterschiede zwischen Rechteck-ROI und manuell erstellten ROI gleicher Größe auftreten. Eine hochsignifikante Trennung zwischen behandelten und unbehandelten Patienten ergab sich für alle untersuchten Auswerteverfahren. Der ermittelte Quotient wird wesentlich durch das Auflösungsvermögen der Kamera und nur relativ geringfügig durch die verwendete ROI-Technik bestimmt. Die Quotienten verschiedener Arbeitsgruppen sind quantitativ nicht miteinander vergleichbar.

Sentinel lymph node biopsy (SLNB) without axillary lymph node dissection (ALND) in SLN negative patients is a standard of care for most breast cancer patients. SLNB for axillary staging after primary systemic therapy (PST) is still under discussion because of possibly reduced accuracy, while data are lacking. The purpose of this study was to evaluate the accuracy of SLNB after PST.A total of 185 breast cancer patients were treated with PST; 160 patients received preoperative chemotherapy, and 25 patients received preoperative endocrine therapy. Thus, 143 of 160 patients with preoperative chemotherapy and 22 of 25 patients with preoperative endocrine therapy were eligible for evaluation. The combination of blue dye and radioactive tracer was used for identification of SLNs. All patients received SLNB and axillary lymph node dissection (ALND). Pathologic assessment of SLNs was performed and compared to non-SLN status.Pathologic complete response rates and breast conserving therapy rates were 15.4 and 78.3% in the preoperative chemotherapy group and 0 and 77.3% in the preoperative endocrine therapy group, respectively. Identification rate, sensitivity, overall accuracy, and false-negative rate were 81.1% (116 of 143), 91.7% (55 of 60), 95.7% (111 of 116), and 8.3% (5 of 60) in the preoperative chemotherapy group and 77.3% (17 of 22), 90.0% (9 of 10), 94.1% (16 of 17), and 10.0% (1 of 10) in the preoperative endocrine therapy group, respectively.SLNB after primary systemic therapy is accurate, and the results are comparable to those of primary SLNB. SLNB after PST could spare ALND in up to 40% of patients with primary positive axillary lymph nodes and should be considered as a standard for axillary staging in those patients.

The combination of ovarian suppression and tamoxifen is a standard adjuvant endocrine therapy in premenopausal women with endocrine-responsive breast cancer. Several reports have demonstrated that adjuvant endocrine therapy with aromatase inhibitors is superior to endocrine therapy with tamoxifen in postmenopausal women with endocrine-responsive breast cancer. The benefits of aromatase inhibitors, however, in premenopausal women are largely unknown. Previous studies showing that bisphosphonate therapy with zoledronic acid had antitumor and antimetastatic properties and prevented aromatase inhibitor-associated bone loss were the basis for the Austrian Breast and Colorectal Cancer Study Group trial 12. This randomized trial was part of the Austrian Breast and Colorectal Cancer Study Group trial 12 and investigated the possible benefits of adding zoledronic acid to adjuvant endocrine therapy with either Anastrozole or Tamoxifen in premenopausal women with endocrine-responsive early breast cancer. After primary surgery, 1803 patients were randomized to receive goserelin plus tamoxifen with (n = 449) or without (n = 451) zoledronic acid or goserelin plus anastrozole with (n = 450) or without (n = 453) zoledronic acid for 3 years. The primary end-point was disease-free survival, defined as the first occurrence of one or more of the following event(s): death from any cause, local or regional relapse, distant metastasis, contralateral breast cancer, and a second primary tumor. Secondary end points were recurrence-free survival and overall survival. At a median follow-up of 47.8 months, 137 events met the criteria for the primary end point. No significant difference in disease-free survival was found between the goserelin/anastrozole and goserelin/tamoxifen groups (92.0% vs. 92.8%, respectively); the hazard ratio (HR) for disease progression was 1.10, with a 95% confidence interval [CI] of 0.78―1.53; P = 0.59. Rates of recurrence-free survival and overall survival also did not differ among the 2 groups. The addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival at 47.8 months; 94.0% of patients receiving zoledronic acid were free of disease compared to 90.8% of those receiving adjuvant endocrine therapy alone (HR, 0.64; 95% CI, 0.46―0.91; P = 0.01). No significant reduction in the risk of death was associated by adding zoledronic acid to adjuvant endocrine treatment (HR, 0.60; 95% CI, 0.32―1.11; P = 0.11). Overall, adverse events were as expected and no increase in serious adverse events or treatment-related deaths occurred. These data show that addition of zoledronic acid to adjuvant endocrine therapy improves disease-free survival in a population of premenopausal women with endocrine-responsive early breast cancer.

Purpose To evaluate the triplet combination of bevacizumab, capecitabine and docetaxel (XTA) as neoadjuvant therapy for breast cancer. Experimental design Patients with invasive, HER2-negative, nonmetastatic breast cancer (T2–4c >2 cm) and no prior systemic therapy received six 21-day cycles of XTA (bevacizumab 15 mg/kg, day 1, cycles 1–5; docetaxel 75 mg/m2, day 1 of each cycle; capecitabine 950 mg/m2 twice daily for 14 days of each cycle). Patients underwent surgery 2–4 weeks after completing XTA, followed by radiotherapy, chemotherapy and hormone therapy according to institution guidelines. Pathologic complete response (pCR), the primary endpoint, was defined as no evidence of invasive tumour in the final surgical sample. Secondary endpoints included rates of clinical response and breast-conserving surgery and safety. Results Median age of the 18 enrolled patients was 48 years (range 34–69). Most patients (72%) received six cycles of neoadjuvant therapy. pCR rate was 22% (95% confidence interval [CI]: 6–48). Nine of the patients without pCR achieved clinical partial response, giving a 72% overall clinical response rate (95% CI: 47–90). Fifteen patients underwent breast-conserving surgery (83%; 95% CI: 59–96). One additional patient had breast-conserving surgery, followed by mastectomy 1 month later. The remaining 2 patients underwent modified radical mastectomy. XTA was reasonably well tolerated, with no unexpected toxicities or treatment-related deaths. Conclusions The 22% pCR rate in a HER2-negative population suggests that addition of bevacizumab increases the activity of neoadjuvant capecitabine–docetaxel. Further evaluation of this regimen in early breast cancer is recommended.