DEGRO practical guideline for partial-breast irradiation.

PURPOSE: This consensus statement from the Breast Cancer Working Group of the German Society for Radiation Oncology (DEGRO) aims to define practical guidelines for accelerated partial-breast irradiation (APBI). METHODS: Recent recommendations for relevant aspects of APBI were summarized and a panel of experts reviewed all the relevant literature. Panel members of the DEGRO experts participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for implementing APBI in clinical routine, focusing on patient selection, target definition, and treatment technique. RESULTS: Appropriate patient selection, target definition for different APBI techniques, and basic rules for appropriate APBI techniques for clinical routine outside of clinical trials are described. Detailed recommendations for APBI in daily practice, including dose constraints, are given. CONCLUSION: Guidelines are mandatory to assure optimal results of APBI using different techniques.

DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences.

OBJECTIVE: To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. METHODS: A comprehensive survey of the literature using the search phrases "locoregional breast cancer recurrence", "chest wall recurrence", "local recurrence", "regional recurrence", and "breast cancer" was performed, using the limits "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guidelines". CONCLUSIONS: Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts depend on the time interval to first radiotherapy, presence of late radiation effects, and concurrent or sequential systemic treatment. Combination with hyperthermia can further improve tumor control. In patients with isolated axillary or supraclavicular recurrence, durable disease control is best achieved with multimodality therapy including surgery and radiotherapy. Radiation therapy significantly improves local control and should be applied whenever feasible.

Discontinuous anchoring transition and photothermal switching in composites of liquid crystals and conducting polymer nanofibers.

We prepared nanocomposites of a nematic liquid crystal and nanofibers of a conducting polymer (polyaniline). All the nanocomposites exhibit a discontinuous surface anchoring transition from planar to homeotropic in the nematic phase on a perfluoropolymer coated surface with a thermal hysteresis (≈ 5.3 °C). We observe a relatively large bistable conductivity and demonstrate a light driven switching of conductivity and dielectric constant in dye doped nanocomposites in the thermal hysteresis (bistable) region. The experimental results have been explained based on the reorientation of the nanofibers driven by the anchoring transition of the nematic liquid crystal. We show a significant enhancement of the bistable temperature range (≈ 13 °C) by an appropriate choice of compound in the binary system.

Effect of smectic short-range order on the discontinuous anchoring transition in nematic liquid crystals.

We report studies on the temperature dependent alignment behavior of a homologous series of trans, trans- 4, 4'-dialkyl-(1α,1' α-bicyclohexyl)-4ß-carbonitrile (CCNs) on a perfluoropolymer coated cells. Among six compounds in the series, one (CCN-35) has only nematic phase and the remaining five have either smectic-A or smectic-B in addition to the nematic phase. We simultaneously performed temperature dependent dielectric measurements and optical polarising microscope observation. It is found that except for CCN-35 and CCN-73, the remaining four compounds exhibit discontinuous anchoring transition from planar to homeotropic and vice versa with increasing thermal hysteresis. We developed a simple theory taking into account the effect of smectic short-range order at the substrates to explain the experimental observations.

DEGRO practical guidelines: radiotherapy of breast cancer III--radiotherapy of the lymphatic pathways.

AIM: The purpose of this work is to update the practical guidelines for adjuvant radiotherapy of the regional lymphatics of breast cancer published in 2008 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO). METHODS: A comprehensive survey of the literature concerning regional nodal irradiation (RNI) was performed using the following search terms: "breast cancer", "radiotherapy", "regional node irradiation". Recent randomized trials were analyzed for outcome as well as for differences in target definition. Field arrangements in the different studies were reproduced and superimposed on CT slices with individually contoured node areas. Moreover, data from recently published meta-analyses and guidelines of international breast cancer societies, yielding new aspects compared to 2008, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the German interdisciplinary S3 guidelines updated in 2012, this paper addresses indications, targeting, and techniques of radiotherapy of the lymphatic pathways after surgery for breast cancer. RESULTS: International guidelines reveal substantial differences regarding indications for RNI. Patients with 1-3 positive nodes seem to profit from RNI compared to whole breast (WBI) or chest wall irradiation alone, both with regard to locoregional control and disease-free survival. Irradiation of the regional lymphatics including axillary, supraclavicular, and internal mammary nodes provided a small but significant survival benefit in recent randomized trials and one meta-analysis. Lymph node irradiation yields comparable tumor control in comparison to axillary lymph node dissection (ALND), while reducing the rate of lymph edema. Data concerning the impact of 1-2 macroscopically affected sentinel node (SN) or microscopic metastases on prognosis are conflicting. CONCLUSION: Recent data suggest that the current restrictive use of RNI should be scrutinized because the risk-benefit relationship appears to shift towards an improvement of outcome.

DEGRO practical guidelines: radiotherapy of breast cancer II: radiotherapy of non-invasive neoplasia of the breast.

PURPOSE: To complement and update the 2007 practice guidelines of the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) for radiotherapy (RT) of breast cancer. Owing to its growing clinical relevance, in the current version, a separate paper is dedicated to non-invasive proliferating epithelial neoplasia of the breast. In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indication and technique of RT in addition to breast conserving surgery. METHODS: The DEGRO expert panel performed a comprehensive survey of the literature comprising recently published data from clinical controlled trials, systematic reviews as well as meta-analyses, referring to the criteria of evidence-based medicine yielding new aspects compared to 2005 and 2007. The literature search encompassed the period 2008 to September 2012 using databases of PubMed and Guidelines International Network (G-I-N). Search terms were "non invasive breast cancer", "ductal carcinoma in situ, "dcis", "borderline breast lesions", "lobular neoplasia", "radiotherapy" and "radiation therapy". In addition to the more general statements of the German interdisciplinary S3 guidelines, this paper is especially focused on indications of RT and decision making of non-invasive neoplasia of the breast after surgery, especially ductal carcinoma in situ. RESULTS: Among different non-invasive neoplasia of the breast only the subgroup of pure ductal carcinoma in situ (DCIS; synonym ductal intraepithelial neoplasia, DIN) is considered for further recurrence risk reduction treatment modalities after complete excision of DCIS, particularly RT following breast conserving surgery (BCS), in order to avoid a mastectomy. About half of recurrences are invasive cancers. Up to 50 % of all recurrences require salvage mastectomy. Randomized clinical trials and a huge number of mostly observational studies have unanimously demonstrated that RT significantly reduces recurrence risks of ipsilateral DCIS as well as invasive breast cancer independent of patient age in all subgroups. The recommended total dose is 50 Gy administered as whole breast irradiation (WBI) in single fractions of 1.8 or 2.0 Gy given on 5 days weekly. Retrospective data indicate a possible beneficial effect of an additional tumor bed boost for younger patients. Prospective clinical trials of different dose-volume concepts (hypofractionation, accelerated partial breast irradiation, boost radiotherapy) are still ongoing. CONCLUSION: Postoperative radiotherapy permits breast conservation for the majority of women by halving local recurrence as well as reducing progression rates into invasive cancer. New data confirmed this effect in all patient subsets-even in low risk subgroups (LoE 1a).

DEGRO practical guidelines: radiotherapy of breast cancer I: radiotherapy following breast conserving therapy for invasive breast cancer.

BACKGROUND AND PURPOSE: The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012. METHODS: A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms "breast cancer", "radiotherapy", and "breast conserving therapy". Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer. RESULTS: Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48-0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75-0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified. CONCLUSION: After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.

When are breast cancer patients old enough for the quitclaim of local control?

BACKGROUND: Although postoperative radiotherapy (RT) after breast-conserving surgery (BCS) halves the 10-year recurrence rate in breast cancer patients through all age groups, the question of whether RT may be omitted and replaced by endocrine therapy for women aged 70 years and older with low-risk factors has recently become an issue of debate. METHODS: Survey of the relevant recent literature (Medline) and international guidelines. RESULTS: Three randomized studies investigating the effect of RT in older women revealed significantly increased local recurrence rates when RT was omitted, and a negative impact on disease-free survival was observed in two of these trials. Despite these findings, in one of the studies omission of RT in women over 70 is recommended, leading to a respective amendment in the guidelines of the American National Comprehensive Cancer Network. Several large retrospective cohort studies analyzing the outcome of patients over 65 years with and without RT have since been published and showed a significantly improved local control in all subgroups of advanced age and stage, which predominantly translated into improved disease-free and overall survival. CONCLUSION: No subgroup of elderly patients has yet been identified that did not profit from RT in terms of local control. Therefore, chronological age alone is not an appropriate criterion for deciding against or in favor of adjuvant RT. The DEGRO breast cancer expert panel explicitly discourages determination of a certain age for the omission of postoperative RT in healthy elderly women with low-risk breast cancer. For frail elderly women, treatment decisions should be individually decided on the basis of standardized geriatric assessment.

Slow magnetic relaxations in manganese(III) tetra(meta-fluorophenyl)porphyrin-tetracyanoethenide. Comparison with the relative single chain magnet ortho compound.

Mn(III) tetra(meta-fluorophenyl)porphyrin-tetracyanoethenide coordination polymer (abbreviated meta-F) was synthesized and crystallographically and magnetically characterized. The compound crystallizes in the space group C2/c with four equivalent molecules in the unit cell arranged along two symmetry related nonparallel linear chain directions. Magnetic properties were studied by SQUID dc magnetization and ac susceptibility techniques and high field-high frequency electron spin resonance (HF-ESR). Glassy transition to a ferromagnetic-like state is observed at 10 K accompanied by slow magnetic relaxations. The glassiness is interpreted as due to 3D domain wall pinning. In a bias dc magnetic field the width of the relaxation time distribution decreases and the relaxations become similar to the relaxations of the single chain magnet Mn(III) tetra(ortho-fluorophenyl)porphyrin-tetracyanoethenide (abbreviated ortho-F), for which comparative HF-ESR studies were also conducted in this work. Magnetic properties of these two compounds are compared, and the nature of magnetic relaxations in meta-F is discussed.

Magnetooptical and structural investigations of five dimeric cobalt(II) complexes mimicking metalloenzyme active sites.

Four novel cobalt(II) complexes mimicking metalloenzyme active sites, novel C(14)H(22)Cl(12)Co(2)O(13)·2C(3)H(8)O (1), C(28)H(36)Cl(24)Co(4)O(28)·4C(4)H(8)O(2) (2), C(16)H(22)Cl(12)Co(2)O(13)·C(2)HCl(3)O(2) (3), C(16)H(22)Cl(12)Co(2)O(13) (4), and one known C(40)H(78)Cl(8)Co(2)O(17) (5) are composed of the same core of two high-spin cobalt(II) centers triply bridged by water and two trichloroacetato (1-4) or two pivalate (5) groups but differ in terminal ligands. The crystal structures of new compounds 1-4 belong to the space groups P ̅1, P2(1)/c, P ̅1, and Pbcn, respectively. All five investigated complexes contain Co atoms in distorted octahedral coordination. The complexes were characterized by magnetic susceptibility and magnetization measurements and by variable-temperature variable-field magnetic circular dichroism spectroscopy. Experimental data were analyzed in the frame of the theoretical model, which includes an unquenched orbital moment of the Co(II) ions. All investigated compounds are antiferromagnetically coupled with exchange constants in the range -1.5 to -2.1 cm(-1). However, there is a significant difference between the crystal-field-splitting parameters.

Exchange-coupled cobalt(II) dimer with unusual magnetic circular dichroism saturation behavior.

The exchange-coupled complex [Co(2)(mu-H(2)O)(mu-OAc)(2)(OAc)(2)(tmen)(2)] (OAc = CH(3)COO(-) acetato; tmen = N,N,N',N'-tetramethylenediamine) has been studied by magnetic circular dichroism (MCD) spectroscopy and magnetization measurements. A peculiar behavior of the MCD spectra was observed with a change in the magnetic field. The intensity of particular lines initially increases, then decreases with an increase in the magnetic field strength, disappears with a further field increase, and appears again with the opposite sign. This behavior was explained by the overlap of the electronic transitions at different but near wavelengths. The obtained MCD magnetization curves, together with magnetization obtained by a SQUID magnetometer, are well reproduced using the Hamiltonian, which takes into account an orbital magnetic moment.

Two-dimensional crystallization conditions of human leukotriene C4 synthase requiring adjustment of a particularly large combination of specific parameters.

Human leukotriene C(4) synthase (LTC(4)S) forms highly ordered two-dimensional (2D) crystals under specific reconstitution conditions. It was found that control of a larger number of parameters than is usually observed for 2D crystallization of membrane proteins was necessary to induce crystal formation of LTC(4)S. Here, we describe the parameters that were optimized to yield large and well-ordered 2D crystals of LTC(4)S. Careful fractioning of eluates during the protein purification was essential for obtaining crystals. While the lipid-to-protein ratio was critical in obtaining order, four parameters were decisive in inducing growth of crystals that were up to several microns in size. To obtain a favorable diameter, salt, temperature, glycerol, and initial detergent concentration had to be controlled with great care. Interestingly, several crystal forms could be grown, namely the plane group symmetries of p2, p3, p312, and two different unit cell sizes of plane group symmetry p321.

Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer.

Breast-conserving surgery followed by radiotherapy is effective in reducing recurrence; however, telangiectasia and fibrosis can occur as late skin side effects. As radiotherapy acts through producing DNA damage, we investigated whether genetic variation in DNA repair and damage response confers increased susceptibility to develop late normal skin complications. Breast cancer patients who received radiotherapy after breast-conserving surgery were examined for late complications of radiotherapy after a median follow-up time of 51 months. Polymorphisms in genes involved in DNA repair (APEX1, XRCC1, XRCC2, XRCC3, XPD) and damage response (TP53, P21) were determined. Associations between telangiectasia and genotypes were assessed among 409 patients, using multivariate logistic regression. A total of 131 patients presented with telangiectasia and 28 patients with fibrosis. Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia. The odds ratios (OR) were 1.66 (95% confidence interval (CI): 1.02-2.72) for 72Pro carriers and 1.95 (95% CI: 1.13-3.35) for PIN3 A2 allele carriers compared with non-carriers. The TP53 haplotype containing both variant alleles was associated with almost a two-fold increase in risk (OR 1.97, 95% CI: 1.11-3.52) for telangiectasia. Variants in the TP53 gene may therefore modify the risk of late skin toxicity after radiotherapy.

Measurement of CD4+ T cells in point-of-care settings with the Sysmex pocH-100i haematological analyser.

The decision to provide antiretroviral therapy to HIV-positive patients mainly depends on the CD4(+) T-cell count, with therapy indicated at a cut-off value of <350-200 CD4(+) T cells/microl blood. Monitoring patients is still a major problem in countries with limited resources where blood samples often have to be transported over long distances to regional referral centres in which the count can be performed on flow cytometers. We have evaluated a newly developed simple and inexpensive method for CD4(+) T-cell quantification. It is a variation of the Invitrogen T4 Quant kit, with manual isolation of nuclei from CD4(+) T cells and subsequent counting on the small haematology analyser pocH-100i, Sysmex. We have demonstrated that this new method is highly reproducible and gives stable and linear results over a wide range of CD4(+) T-cell concentrations. Method comparison to two different flow cytometers showed excellent correlation with concordances of about 93%. Overall, this method is rapid, easy to perform and offers a good reliable alternative to measurement by flow cytometry. The pocH-100i has the additional benefit of providing a complete blood count with a three-part white blood cell differential and software for patient data storage and handling.

Extended triple-bridged Ni(II)- and Co(II)-hydroxamate trinuclear complexes: synthesis, crystal structures, and magnetic properties.

Crystal structures of new trinuclear complexes [Ni 3(mu-OAc F) 4(mu-AA) 2(tmen) 2], [Ni 3(mu-OAc F) 4(mu-BA) 2(tmen) 2], and [Co 3(mu-OAc F) 4(mu-BA) 2(tmen) 2] have been determined (OAc F = CF 3COO (-), AA = acetohydroxamate anion, BA = benzohydroxamate anion, tmen = N, N, N', N'-tetramethylethylenediamine). In each structure, the metal ions have distorted octahedral coordination and are triply bridged by one hydroxamate and two trifluoroacetate bridges. Magnetic properties of these compounds and of relative [Co 3(mu-OAc F) 4(mu-AA) 2(tmen) 2] were studied by susceptibility and magnetization measurements. It was shown that for nickel trimers the intramolecular magnetic coupling is weak ferromagnetic in the case of the complex with the AA group, and there is nearly no coupling in the case with BA group. Rather large zero field splitting was obtained for the distorted octahedral environments of the terminal nickel ions. The cobalt trimers were additionally studied by magnetic circular dichroism (MCD) measurements. The exchange interaction of the cobalt complexes is antiferromagnetic.