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Background The effects of intravenous immunoglobulin G replacement on perceived health and infection susceptibility of patients suffering from immunoglobulin G (IgG) deficiencies should be evaluated in a prospective analysis. Methods Patients with symptomatic primary or secondary IgG deficiencies were interviewed prior to the first IgG infusion (t0) and over the course of their treatment (t1 - t6). The respondents rated their current health using a 100 point scale (EQ-5D-5L), ranging from 0 (‘worst imaginable health’) to 100 (‘best imaginable health’). The patients also provided information on the frequency of infections and of infections requiring antibiotics in the past 8 weeks. A healthy control group (CG) without oncologic diseases answered the questions once. Results One hundred six patients with a median age of 65 years (21–85 years) were investigated. The median serum IgG concentration changed from 500 mg/dl (t0) to 772 mg/dl (t6). The mean number of infections and of infections requiring antibiotics decreased during IgG replacement significantly. Current health according to EQ-5D-5L improved from 57 (t0) to 68 (t6), compared to 73 in the CG. Conclusion During the course of IgG replacement patients reported fewer and less severe infections. Their health assessment improved but still was inferior to the healthy CG.

Introduction: The aim of shared decision making (SDM) is a treatment decision in which patients are meaningfully involved. Many preference-sensitive decisions have to be made in breast cancer treatment and little is known about the implementation of SDM. We therefore investigated the process of SDM in routine care treatment. Methods: All breast cancer patients who underwent surgery in four German breast centers between 07/2016 and 07/2018 were invited to take part. The experienced decision-making process was assessed using the German version of the 9-item SDM questionnaire (PEF-FB-9). Furthermore, satisfaction with care with focus on patient participation was assessed using the ZAPA questionnaire. PEF-FB-9 and ZAPA items were summed up and transformed into a total score ranging from 0 to 100. The higher the total score the higher the experienced degree of participation and satisfaction, respectively. Participants were asked to separately rate decision-making consultations with their inpatient hospital doctors, outpatient gynecologists, outpatient oncologists and primary care providers (PCP). In addition, satisfaction with decision, participation preferences as well as other items for the complete decision process were queried. Results: Of 1,068 approached patients, 563 with a median age of 62 (31-92) filled in the survey (response rate: 53%). 81% had breast conserving surgery, 19% mastectomy. Consultations were assessed most often for hospital doctors (n=484). Gynecologists (n=270), oncologists (n=174) and PCP (n=64) were evaluated less often. Hospital doctors (mean (M): 75, standard deviation (SD): 22) and oncologists (M: 74, SD: 22) achieved the highest PEF-FB-9 scores indicating the highest degree of SDM. Gynecologists and PCP were rated almost as good with mean scores of 71 (SD: 23) and 69 (SD: 28), respectively. The mean score for all groups of doctors was 74 (SD: 21), less than 4% of patients reported SDM scores Citation Format: Rudolf Weide, Isabelle Scholl, Jan Dünnebacke, Marcus Schmidt, Arno Franzen, Walter Ernst, Ilhan Saka, Heike Spaderna, Stefan Feiten. Shared decision making (SDM) in routine care treatment of breast cancer patients - A survey of patients following surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-12-06.

Introduction: 18,000 women die due to metastatic breast cancer in Germany per year. Median survival is 20–28 months after diagnosis. The question we wanted to answer was whether survival has improved in routine care? Methods: Retrospective analysis of all patients with metastatic breast cancer who were treated between 06/1995-12/2017 in 5 community-based oncology group practices in Germany. Results: 1,321 patients were analyzed with a median age of 62 (23–100). Localizations of metastases were distributed as follows: 49% visceral, 33% bone, 6% CNS, 12% others. 79% were hormone-receptor-positive, 20% Her2-positive, 9% triple-negative. Median overall survival was 37 months (95% Confidence Interval: 34–40), survival probability after 5 years 32.5%. Survival was significantly correlated with localizations of metastases, number of metastasized organs, disease free survival since initial diagnosis, hormone- and Her2-receptor status and age. Patients with hormone-receptor-positive tumors had a median overall survival of 39 months, Her2-positive patients of 45 months and triple-negative patients of 20 months. 86% of hormone-receptor-positive patients received antihormonal therapy. 81% of Her2-positive patients received anti-Her2 therapy. Overall survival according to treatment period 1995-2000, 2001-2005, 2006-2011, 2012-2017 was 34, 35, 37 and 38 months respectively. OS of patients with hormone-positive tumors according to treatment period was 35, 43, 38, and 42 months respectively. OS of patients with Her2-positive tumors according to treatment period was 39, 29, 51, and 54 months respectively. OS of patients with triple-negative tumors according to treatment period was 7, 11, 16, and 25 months respectively. Conclusions: Improved survival of patients with metastatic breast cancer in routine care is strongly restricted to hormone receptor- and Her2-positive tumors most likely due to improved targeted therapies directed against the estrogen-receptor and Her2. Citation Format: Weide R, Rendenbach B, Laubenstein H-P, Braun U, Hünermund K, Burkhard O, Ehscheidt P, Feiten S, Chakupurakal G, Friesenhahn V, Kleboth K, Köppler H, Lutschkin J, Thomalla J, van Roye C, Heymanns J. Improved survival of patients with metastatic breast cancer in routine care is restricted to tumors with positive hormone receptor and/or Her2-expression. Survival analysis of 1,321 patients treated between 1995 and 2017 in oncology group practices [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-16-06.

Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital.A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype.Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus60 years: hazard ratio (HR) 1.63, P0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups.We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.

Seven hundred and twenty-four CLL-outpatients with a median age of 67 (35-92) were analyzed. Four hundred and twenty-seven (59%) were male, 297 (41%) female. At diagnosis 556 (77%) were in Binet stage A, 91 (13%) stage B and 36 (5%) stage C. Forty-six percent received treatment during the evaluation period. Treatment consisted of purine analogs in 38%, alkylating agents in 96%, chemoimmunotherapy with anti-CD20 monoclonal antibodies in 63%, ibrutinib in 9%, venetoclax in 1% and idelalisib in 3%. 3% received allogeneic hematopoietic stem cell transplantation. Overall survival (OS) according to Binet stage was: A 13.9 years (0.1-37.4), B 9.2 years (1.4-29.3) and C 7.9 years (0.5-19.4) respectively. Median OS from the start of therapy improved over time; 1995-2001: 5.8 years, 2002-2008: 6.1 years and 2009-2017: median not reached. Survival of patients with CLL has improved in routine care and was strongly related to active disease, disease stage, performance status and whether therapy included an anti-CD20 monoclonal antibody.

Introduction: The aim of shared decision making (SDM), defined as an interaction between patient and attending physician(s), is a treatment decision in which patients are meaningfully involved. Based on mutual agreement and active participation the awareness of a choice should be created and the choice respected. Many preference-sensitive decisions have to be made in breast cancer treatment. However, little is known about the implementation of SDM in German breast cancer care. We therefore investigated the process of SDM from the patients' perspective. Methods: All breast cancer patients who underwent surgery in one of four certified breast cancer centers in Germany between 07/2016 and 12/2016 were invited by mail to participate in the survey. The experienced decision-making process was assessed using the 9-item Shared Decision Making Questionnaire (SDM-Q-9). SDM-Q-9 items were rated on a 6-point scale ranging from "completely disagree" to "completely agree", added together and transformed into a scale ranging from 0 to 100. The higher the total score the higher the experienced degree of participation in the decision-making process. The survey also assessed patients' satisfaction with treatment, satisfaction with decisions and decisional control preferences, and included a range of demographic and clinical questions. For most items we asked the participants to separately rate decision-making consultations with their inpatient hospital doctors, outpatient gynecologists, outpatient oncologists and primary care providers (PCP). The project is still ongoing, data of approximately 300 patients will be presented at the meeting in December. Results: Of 289 patients approached by mail, 143 filled in the survey (response rate: 49%). Median age at the time of the survey was 62 years (36-89). 83% had breast conserving surgery, 17% mastectomy. 74% were treated with radiation, 31% received neo-/adjuvant chemotherapy. 14% were off-treatment at the time of survey participation, 67% still received antihormonal therapy, 9% anti HER2 treatment, 7% chemotherapy and 2% radiation. Inpatient hospital doctors achieved the highest SDM-Q-9 score (mean of 75, standard deviation of 22) indicating the highest degree of SDM. Oncologists, gynecologists and PCP were rated quite comparable with a mean score of 72 each and standard deviations (SD) of 27, 22 and 31. The mean score for all groups of doctors was 73. For items concerning satisfaction with quality and amount of doctors' information and participation in medical decisions patients showed a high degree of satisfaction, resulting in mean values of 3.6 and 3.5 with SD of 0.6 on a 4-point scale ranging from "1" "very unsatisfied" to "4" "very satisfied". Conclusions: A considerable number of patients took part in the survey. Overall, patients reported to have experienced SDM in many situations where treatment decisions were necessary. Patients were quite satisfied with the quality of information and their participation in medical decisions. However, we do not know whether non-respondents might have had different experiences regarding their treatment decision-making. Further research should include SDM expert observations of breast cancer treatment decisions to validate these findings. Citation Format: Feiten S, Scholl I, Schmidt M, Dünnebacke J, Franzen A, Ernst W, Weide R. Shared decision making (SDM) in routine care treatment of breast cancer patients – a survey of patients following surgery [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-11-07.

Introduction: Currently, about 360 000 breast cancer patients who could, after completion of their primary therapy, take advantage of follow-up options are living in Germany. Up to now very little is known about the extent to which the available options are used and as to how the follow-up reality is experienced and evaluated. Thus, an explorative examination among the patients and their physicians was undertaken. Patients and Methods: All patients who underwent surgery in a certified breast centre between 2007 and 2013 received a standardised questionnaire; at the same time the physicians responsible for the follow-up were invited to answer a standardised questionnaire. Results: 920 patients (response rate: 61 %) with a median age of 65 years (32–95) could be analysed. 99 % of the participants stated that they regularly attended follow-ups. The personal contact with the physician (mean value: 4.4) and the reassurance that the cancer disease had not recurred (mean value: 4.5) were described on a scale of 0 to 5 to be two of the most important factors of the follow-up. Deficits were expressed with regard to psychosocial care (70 %) and the perception and treatment of physical complaints (55 %). In addition, 105 physicians returned completed questionnaires (response rate: 12 %). For asymptomatic patients the physicians performed the following examinations most frequently: anamnesis (92 %), physical examination (87 %) as well as laboratory tests (63 %) and tumour marker determinations (40 %). Conclusion: On the whole it became clear that the vast majority of the patients took advantage of the follow-up options. From the patientʼs perspective the importance of the follow-up lies in contact to the physician and the comforting assurance that the breast cancer has not relapsed. Deficits are seen in the psychosocial care and the perception and treatment of physical impairments. Not recommended examinations were employed by a significant proportion of the surveyed physicians.

Background: The incidence of brain metastases (BM) in breast cancer patients is rising and has become a major clinical challenge. So far, limited therapeutic options and insights into the biology of BM exist since only a few studies analyzed exclusively data of breast cancer patients. In order to improve this situation, our multicenter registry was initiated in 2014: Brain Metastases in Breast Cancer Network Germany (BMBC, GBG79). Materials and Methods: Patients with BM diagnosed since 2000, a history of breast cancer and no history of other malignant or neurologic disease can be included. Registration is allowed retrospectively as well as prospectively into a web–based database ("MedCodes"). Characteristics of the primary tumor, metastatic disease and BM as well as treatment details are documented. For this first analysis, 548 patients from 39 German centers were included. Results: Median age at first diagnosis of BM was 55 years (25 – 90 years). 43% of patients (233/548) were HER2 positive, 19% (n=105) were triple–negative and 25% (n= 138) had luminal primary tumors indicating a selection of patients with specific tumor biology who develop BM. 54 % of the patients (n=267) had up to three BM whereas 45% (n=223) had more than three BM. 19% of patients (n=106) had BM without evidence of extracranial disease. 27% of the patients (n=146) underwent surgery of the BM. Of these patients, 61% (n= 89) were treated with whole brain radiotherapy and 16% (n=23) with stereotactic radiotherapy. In patients without surgery (n=397), 73% (n=289) received whole brain radiotherapy and 7% (n=28) stereotactic radiotherapy. Median time from diagnosis of primary breast cancer to BM was 38.5 month for the entire cohort (CI95% 35.4 – 43.3). The time from first diagnosis to BM was shorter for triple–negative patients (20.9 month, CI95% 15.5 – 25.9) compared with patients with HER2–positive (37.0 month, CI95% 30.5 – 42.0) or luminal tumors (48.3 month, CI95% 38.2 – 54.0) (p Conclusion: This is so far the largest analysis of breast cancer patients with BM treated in Germany. In this cohort, triple–negative subtype or more than three BM were associated with shorter survival from the diagnosis of BM. HER2 positive patients with no HER2 directed therapy after the diagnosis of BM showed a shorter survival. The recruitment of the registry is ongoing and we aim to include more than 1000 patients by the end of 2015. Citation Format: Witzel I, Loibl S, Laakmann E, Augustin D, Flock F, Dohmen H-H, Durmus G, Frank M, Hesse T, Ignatov A, Kühn T, Neunhöffer T, Park-Simon T-W, Schmidt M, Stefek A, Weide R, Würschmidt F, Fehm T, Moebus V, von Minckwitz G, Burchardi N, Mueller V. Brain metastases in breast cancer network Germany (BMBC, GBG 79): First analysis of 548 patients from the multicenter registry. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-08.

Introduction: Breast cancer treatment leads to long-lasting impairments which, according to international guidelines, have to be identified and treated in follow-up care. It remains unclear how follow-up care is perceived by patients and if all needs are met in routine care. Methods: All breast cancer patients who underwent surgery in a German breast cancer centre from 2007 to 2013 were asked to fill out a standardized scanner-readable questionnaire. Medical data were retrieved from their charts and statistically analyzed together with the questionnaire responses. Physicians who could possibly care for breast cancer patients after primary therapy were invited to fill out a standardized scanner-readable questionnaire as well. Results: 920 questionnaires were filled out and returned (response rate: 61%) by patients. Median age at the time of the survey was 65 years (32-95). 58% of patients still received some form of therapy, 94% of them hormonal therapy. 94% were still in follow-up care, 5% stopped and 1% never went. Intervals of follow-up visits suggested by international guidelines were assessed as "quite right" in 93%. The following examinations were conducted throughout the whole follow-up period at least once: physical examination (93%), mammography (90%), sonography of breast (81%) and liver (22%), laboratory (56%), tumor marker (23%), bone scan (21%), MRI (20%) and CT (15%). Different items were rated on a 6-point scale ranging from "0" "not true at all" to "5" "completely true". Follow-up care was regarded as very important for the own health (4.7), reassuring and calming (4.5), well-being to be looked after (4.4) and well cared for (4.4). A continuous contact between patient and doctor was appreciated (4.4). Visits were connected only to a part with distress (2.1), the median score on the NCCN distress thermometer was 4 (0-10). 105 questionnaires were answered by healthcare professionals (response rate 12%), most of them general practitioners (51%) or gynecologists (30%). Doctors carried out or referred asymptomatic patients most often to the following examinations: medical history taking (92%), physical examination (87%), blood chemistry (63%) and tumor markers (40%). Mammography was mentioned in 45%, sonographic examinations of breast, liver and axilla in 49%, 45% and 38%, respectively. 55% were (very) satisfied with international guidelines on follow-up care. Intervals and duration of follow-up visits were assessed as "quite right" in 88% and 60%, respectively. Different items were rated on a 6-point scale ranging from "0" "not important at all" to "5" "very important". Detection of disease recurrence and secondary tumors (4.8), reassurance of patients (4.7) and detection of treatment toxicities (4.5) were assessed as most important aims in follow-up care. Conclusions: An overwhelming majority of patients makes use of follow-up care. Most important qualities from the patient's perspective are reassurance, a feeling of security, calming and continuous care by their doctor. Examinations which are not recommended in international guidelines are used by a considerable amount of healthcare providers. Citation Format: Weide R, Feiten S, Friesenhahn V, Heymanns J, Köppler H, Meister R, van Roye C, Thomalla J, Wey D, Dünnebacke J. Follow-up care of breast cancer patients who were treated in a German breast cancer centre - Survey of patients and attending physicians and analysis of treatment data. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-13.

Supplemental Digital Content is available in the text, Fludarabine, cyclophosphamide and rituximab (FCR) was compared to bendamustine and rituximab (BR) in an international, randomized, open label, phase 3 trial in 561 previously untreated, fit patients with chronic lymphocytic leukemia (CLL) without del (17p). Primary endpoint was progression free survival (PFS). The final primary endpoint analysis after 37.1 months median follow up failed to show the non-inferiority of BR as compared with FCR. With extended median follow up of 58.2 months, median PFS was 42.3 months in BR-treated patients versus 57.6 months for FCR-treated patients (Hazard Ratio [HR] 1.593; 95% CI 1.271–1.996; p 65 years, median PFS was 48.5 months with BR versus 57.9 months with FCR without reaching statistical significance (HR 1.352; 95% CI 0.912–2.006; p = 0.134). Median OS was not reached for both arms with 5-year OS rates of 80.1% vs 80.9%, respectively (HR 1.108; 95% CI 0.755–1.627; p = 0.599). No statistically significant difference was found in the time to secondary malignancy between the 2 groups (at 5 years, 86.6% free from secondary malignancies in the BR group vs 83.8% in the FCR group [HR 0.801; 95% CI 0.507–1.267; p = 0.344]). In patients >65 years secondary neoplasia occurred more frequently after FCR treatment [28 of 86 (32.6%) patients] as compared with BR [18 of 107 (16.8%) patients; p = 0.011]. Health-related quality of life was similar in both treatments. Despite the improved PFS for FCR, OS did not differ. These results also suggest an increase in secondary neoplasia associated with FCR in elderly fit CLL patients.

Late blight disease caused by the plant pathogenic oomycete pathogen

Late blight disease caused by the plant pathogenic oomycete pathogen Phytophthora infestans is one of the most limiting factors in potato production. P. infestans is able to overcome introgressed late blight resistance by adaptation of effector genes. AVR1 is an RXLR effector that triggers immune responses when recognized by the potato resistance protein R1. P. infestans isolates avirulent on R1 plants were found to have AVR1 variants that are recognized by R1. Virulent isolates though, lack AVR1 but do contain a close homologue of AVR1, named A-L, of which all variants escape recognition by R1. Co-expression of AVR1 and R1 in Nicotiana benthamiana results in a hypersensitive response (HR). In contrast, HR is not activated when A-L is co-expressed with R1. AVR1 and A-L are highly similar in structure. They share two W motifs and one Y motif in the C-terminal part but differ in the T-region, a 38 amino acid extension at the carboxyl-terminal tail of AVR1 lacking in A-L. To pinpoint what determines R1-mediated recognition of AVR1 we tested elicitor activity of AVR1 and A-L chimeric and deletion constructs by co-expression with R1. The T-region is important as it enables R1-mediated recognition of A-L, not only when fused to A-L but also via trans-complementation. Yet, AVR1 lacking the T-region is still active as an elicitor of HR, but this activity is lost when certain motifs are swapped with A-L. These data show that A-L circumvents R1 recognition not only because it lacks the T-region, but also because of differences in the conserved C-terminal effector motifs.

Background In a single-center retrospective donor versus no-donor comparison, we investigated if allogeneic stem cell transplantation (alloSCT) can improve the dismal course of poor-risk chronic lymphocytic leukemia (CLL). Patients and methods All patients with CLL who were referred for evaluation of alloSCT within a 7-year time frame and had a donor search indication according to the EBMT criteria or because of Richter's transformation were included. Patients for whom a matched donor could be found within 3 months (matches) were compared with patients without such a donor (controls). Primary end point was overall survival measured from the 3-month landmark after search initiation. Results Of 105 patients with donor search, 97 (matches 83; controls 14) were assessable at the 3-month landmark. Matches and controls were comparable for age, gender, time from diagnosis, number of previous regimens, and remission status. Disregarding if alloSCT was actually carried out or not, survival from the 3-month landmark was significantly better in matches versus controls [hazard ratio 0.38, 95% confidence interval (CI) 0.17–0.85; P = 0.014]. The survival benefit of matches remained significant on multivariate analysis. Conclusion This study provides first comparative evidence that alloSCT may have the potential to improve the natural course of poor-risk CLL as defined by the EBMT criteria.

The actin cytoskeleton is conserved in all eukaryotes, but its functions vary among different organisms. In oomycetes, the function of the actin cytoskeleton has received relatively little attention. We have performed a bioinformatics study and show that oomycete actin genes fall within a distinct clade that is divergent from plant, fungal and vertebrate actin genes. To obtain a better understanding of the functions of the actin cytoskeleton in hyphal growth of oomycetes, we studied the actin organization in Phytophthora infestans hyphae and the consequences of treatment with the actin depolymerising drug latrunculin B (latB). This revealed that latB treatment causes a concentration dependent inhibition of colony expansion and aberrant hyphal growth. The most obvious aberrations observed upon treatment with 0.1 μM latB were increased hyphal branching and irregular tube diameters whereas at higher concentrations latB (0.5 and 1 μM) tips of expanding hyphae changed into balloon-like shapes. This aberrant growth correlated with changes in the organization of the actin cytoskeleton. In untreated hyphae, staining with fluorescently tagged phalloidin revealed two populations of actin filaments: long, axially oriented actin filament cables and cortical actin filament plaques. Two hyphal subtypes were recognized, one containing only plaques and the other containing both cables and plaques. In the latter, some hyphae had an apical zone without actin filament plaques. Upon latB treatment, the proportion of hyphae without actin filament cables increased and there were more hyphae with a short apical zone without actin filament plaques. In general, actin filament plaques were more resilient against actin depolymerisation than actin filament cables. Besides disturbing hyphal growth and actin organization, actin depolymerisation also affected the positioning of nuclei. In the presence of latB, the distance between nuclei and the hyphal tip decreased, suggesting that the actin cytoskeleton plays a role in preventing the movement of nuclei towards the hyphal tip.

Objectives: Evaluation of the subjectively experienced physical, psychological, social and job-related consequences of breast cancer. Methods: Standardized paper pencil interview of patients with the initial diagnosis of breast cancer who had their primary surgery between 01/2006 and 12/2010 at an accredited breast cancer centre followed by systemic adjuvant treatment. The data collection was conducted with the help of a self-developed scanner-readable questionnaire which had been evaluated in a pretest. Results: 1260 patients were contacted, 871 completed questionnaires (return rate 72%) were analyzed. Median age of the patients (99.5% women) at the time of the interview was 65 years (30–91). 6% relapsed during the observation period. 91% were “satisfied” or “very satisfied” with the surgical result. 67% indicated a complete freedom of pain. 23% received lymphatic drainage at the time of the questioning (11/2011), 33% complained about limitations of arm and/or shoulder function. 76% received anti-hormonal therapy, 13% stopped the anti-hormonal medication prematurely. Patients received a mean of 1.3 different anti-hormonal therapies, 54% took Tamoxifen. Psychological distress, cognitive limitations and physical consequences were rated on a scale from 1 – “not at all” to 4 – “very much”. The highest average values were found for the items sleep disturbances (2.3) and exhaustion (2.3), the lowest for depression (1.7) and word-finding difficulties (1.8). After therapy only 39% described a complete recovery of their physical capacity, 62% regained their previous mental capacity. 44% were in employment before their disease. 67% returned to their workplace but only 65% of them with their previous number of hours. 15% indicated disadvantages in their workplace due to the breast cancer disease. For 75% their partnership did not change, 12% experienced a deterioration, 13% an improvement. Before the illness 9% consulted a psychiatrist/psychotherapist, after the illness 18%. Before the diagnosis of breast cancer 13% received antipsychotic drugs, after the disease 25%. Conclusions: Breast cancer diagnosis and therapy leads to long lasting impairment of physical, psychological, social and job-related functioning in a significant number of patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-11.

Introduction: It is well-known that people who care for patients with a metastatic carcinoma are exposed to an above-average level of psychosocial distress. No data are available concerning the distress of main care-givers of female patients with metastatic breast cancer, who are treated in a community based oncology group practice. Methods: Standardized cross-sectional survey of main care-givers and patients with metastatic breast cancer who were treated in a community based oncology group practice in Germany between 04/2010-03/2011. Psychosocial distress of the patients and their main care-givers were evaluated using the German versions of the Distress Thermometer (DT) and the Problem List (PL). In addition anxiety and depression of the main care-givers were assessed using the Hospital Anxiety and Depression Scale (HADS-D). Results: 83 female patients with a median age of 65 (41-93) were interviewed. 6% did not have a main care-giver, 7% indicated that they needed no support, 48% reported one main care-giver and 39% several. Partners (60%), children (47%), siblings (11%) and friends (10%) were the most important care-givers. 47% of patients preferred visiting the practice in companion with their care-givers. The patients’ median score on the DT was 5 (0-10), with 34% scoring above cut-off (> 5) for psychosocial distress. 52 main care-givers (61% male, 39% female) with a median age of 57.5 (41-86) were interviewed. The relationships to the patients were as follows: partners 62%, children 27%, mothers, siblings and friends each with 4%. The main care-givers themselves were supported by partners (54%), children (21%) friends (17%) and siblings (8%), 23% did not receive any support. The median score on the DT was 5 (0-10), with 44% scoring above cut-off (> 5) for psychosocial distress. According to the HADS-D 37% (cut-off ≥ 8) of the care-givers reported anxiety, with a mean score of 6.6 (0-14). 15% could be regarded as depressed (cut-off ≥ 8), with a mean score of 4.1 (0-15). Conclusions: The main care-givers are distressed even more than the patients themselves. 37% of care-givers reported anxiety; depression can be observed too, but less frequently in 15%. Both issues should be addressed by healthcare professionals. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-17-01.

Background: Systematic evaluation of psychosocial distress in oncology outpatients is an important issue. We assessed feasibility and benefit of standardized routine screening using the Distress Thermometer (DT) and Problem List (PL) in all patients of our community-based hematooncology group practice. Patients and methods: One thousand four hundred forty-six patients were screened between July 2008 and September 2008. Five hundred randomly selected patients were sent a feedback form. Results: The average distress level was 4.7, with 37% indicating a distress level >5. Patients with nonmalignant diseases (81% autoimmune diseases or hereditary hemochromatosis) showed the highest distress level of 5.2. Most distressed were patients who just learned about relapse or metastases (6.4), patients receiving best supportive care (5.4) and patients receiving adjuvant antihormonal therapy (5.4). Ninety-seven percent of patients appreciated to speak to their doctor about their distress. Fifty-six percent felt better than usual after this consultation. Conclusion: DT and PL are feasible instruments to measure distress in hematooncology outpatients receiving routine care. DT and PL are able to improve doctor–patient communication and thus should be implemented in routine patient care. The study shows that distress is distributed differently between individuals, disease groups and treatment phases.

KOPPLER H., HEYMANNS J., THOMALLA J., KLEBOTH K. & WEIDE R. (2010) European Journal of Cancer Care19, 795–802 The impact of new treatment options for advanced colorectal cancer on routine care: results of a retrospective analysis of 206 consecutive patients treated in a community-based oncology group practice in Germany Due to necessary selection criteria, the results obtained in clinical trials may not reflect the actual impact of current treatment options for unselected general populations. We analysed the treatment modalities and the outcome in 206 consecutive patients with advanced colorectal cancer who started treatment between 1/1999 and 11/2004. The median age of this cohort was 66 years (range 30–87) and 39 patients (19%) were ≥75 years old. First-line treatment consisted of low-dose bolus 5-fluorouracil and folinic acid regimens in 68 patients (33%), weekly 24-h 5-fluorouracil infusion and folinic acid in 36 patients (17%), weekly 24-h 5-fluorouracil infusion plus oxaliplatin or irinotecan in 60 patients (29%), capecitabine regimens in 22 patients (11%), monotherapy with oxaliplatin or irinotecan in six patients (3%) and other regimens in 14 patients (7%). A total of 166 patients (81%) received a second-line treatment and third-line chemotherapy was given to 122/206 patients (59%). With a minimum follow-up of 18 months, the median survival of the cohort is 21 months (range 1–85) and 17 months (range 3–57) for patients ≥75 years. We conclude that the increased survival seen in prospective studies can be transferred to routine care for unselected patients with advanced colorectal cancer.

Abdominal sonography is now the most frequently used screening method for the detection of abdominal lymph node enlargement. For proper classification, size, localisation and infiltration pattern must be known. The definitive determination whether lymph nodes are benign or malignant cannot be made by the size of the lesion alone. The localisation (parietal/visceral) of enlarged lymph nodes has been shown to be of significance in the staging of abdominal carcinomas. Different infiltration patterns (diffuse small nodular, focal small nodular, focal large nodular, bulky formations) show the broad spectrum of abdominal lymphomas detected by ultrasound. Knowledge of these different infiltration patterns together with clinical information often helps to discriminate between lymph node enlargement caused by inflammation, metastasis, or malignant lymphoma. The definitive diagnosis is made via laparotomy, ultrasound guided biopsy or sonographic follow-up studies.

Infections are major complications in chronic lymphoproliferative disorders, among them indolent non-Hodgkin's lymphoma (iNHL) including chronic lymphocytic leukemia, follicular lymphoma and multiple myeloma.We report on a retrospective cohort analysis of outpatients with indolent non-Hodgkin's lymphoma who were treated in an oncology / hematology group practice and received intravenous polyvalent immunoglobulin G (IVIG) as supportive care. The aim was to describe the treated iNHL population, the course of therapy and the effects of IVIG administrations on the levels of immunoglobulin G (IgG), the incidence of infections and the survival time.57 patients with secondary iNHL antibody deficiencies (n = 46) or IgG subclass deficiencies (n = 11) who received IVIG substitution were included. Patients received median 11 IVIG doses with a mean dose of 28 g over a period of median 9.5 months.Mean IgG levels increased with IVIG substitution at about twice and then remained within the normal range. The incidence of infections decreased in 46 % of treated patients. Effects on survival could not be observed. Median overall survival was in the group of substituted patients 124 months (range 7-124), the control group had a median survival time of 96 months (range 3-129) (p = 0.537).IgG levels should be reviewed during IVIG substitution on a regular basis and dosage and intervals should be adjusted individually.

Late blight caused by the plant pathogenic oomycete Phytophthora infestans is known as one of the most destructive potato diseases. Plant breeders tend to employ NB-LRR-based resistance for introducing genetically controlled late blight resistance in their breeding lines. However, P. infestans is able to rapidly escape this type of resistance, and hence, NB-LRR-based resistance in potato cultivars is often not durable. Previously, we identified a novel type of Phytophthora resistance in Arabidopsis. This resistance is mediated by the cell surface receptor LecRK-I.9, which belongs to the family of L-type lectin receptor kinases. In this study, we report that expression of the Arabidopsis LecRK-I.9 gene in potato and Nicotiana benthamiana results in significantly enhanced late blight resistance. Transcriptional profiling showed strong reduction in salicylic acid (SA)-mediated defence gene expression in LecRK-I.9 transgenic potato lines (TPLs). In contrast, transcripts of two protease inhibitor genes accumulated to extreme high levels, suggesting that LecRK-I.9-mediated late blight resistance is relying on a defence response that includes activation of protease inhibitors. These results demonstrate that the functionality of LecRK-I.9 in Phytophthora resistance is maintained after interfamily transfer to potato and N. benthamiana and suggest that this novel type of LecRK-based resistance can be exploited in breeding strategies to improve durable late blight resistance in Solanaceous crops.

A model for transepithelial migration of human fungal pathogens was established, in which Candida albicans was shown to migrate across a monolayer of Caco-2 intestinal cells in a two-chamber system. Electron microscopy revealed typical stages of epithelial penetration by C. albicans including phagocytosis at the apical side, intra- and intercellular migration and exit on the basolateral side of the monolayer. Hyphal growth forms appeared particularly involved in penetration of the Caco-2 monolayer. The model was examined using defined C. albicans mutants defective in hyphal development (efg1/efg1) or growth (ura3/ura3). Transmigration of the efg1/efg1 mutant strain was reduced, while transmigration of the ura3/ura3 strain was blocked completely in the absence of uridine. Because these results parallel virulence characteristics of the mutants the Caco-2 monolayer system appears a useful model for the study of fungal-human host cell interactions.

The AVR9 peptide of the fungal pathogen Cladosporium fulvum and the INF1 protein of the oomycete pathogen Phytophthora infestans elicit the hypersensitive response (HR) on Cf9 tomato or Cf-9 transgenic tobacco and on all cultivars of tobacco, respectively. Expression of either the functional Avr9 or inf1 genes from engineered potato virus X (PVX) genomes resulted in localized HR lesions on tobacco plants responsive to the elicitors and inhibited spread of the recombinant virus. In contrast, PVX derivatives producing mutant forms of AVR9 and INF1 with reduced elicitor activity caused systemic necrotic and/or mosaic symptoms, and were unable to inhibit PVX spread. These results demonstrate that HR is a highly versatile defense mechanism active against unrelated pathogens irrespective of the HR-inducing agent, and that resistance to recombinant PVX in tobacco is correlated with the strength of the transgene-encoded elicitor.

Integration of molecular and classical genetic maps is an essential requirement for marker-assisted breeding, quantitative trait locus mapping and map-based cloning. With respects to tomato, such maps are only available for the top part of chromosome 1, for chromosome 3 and for the short arm and the centromere proximal part of the long arm of chromosome 6. Employing an L. esculentum line carrying an L. hirsutum introgression we constructed an integrated linkage map for the telomere proximal part of the long arm of tomato chromosome 6, thereby completing the integrated map published previously. With an average map distance of only 0.6 cM the map provides detailed information on the relative position of molecular markers and several traits of economical importance, such as the fruit color marker B. Furthermore, two additional crosses using lines containing L. pennellii introgressions were performed to address the question as to how the recombination frequency in a marked interval on the long arm of chromosome 6 is affected by introgressed segments from different origins. It is concluded that recombination is not merely affected by the local level of homology but also by surrounding sequences. Combination of all the linkage data generated in various crosses described in this and other studies enabled the construction of the first integrated map of an entire tomato chromosome. This map carries 42 loci and shows the position of 15 classical genes relative to 59 molecular markers.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan-Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

We have previously presented an integrated linkage map of tomato chromosome 6, that showed the position of restriction fragment length polymorphism (RFLP) and randomly amplified polymorphic DNA (RAPD) markers relative to a variety of classical markers. As for the short arm, map resolution has now been improved by crossing the chromosome 6 substitution line WSL6 to additional tester lines, carrying markers on the short arm. Molecular linkage analysis of the F2 populations enabled us to produce an integrated linkage map showing the position of molecular markers relative to the classical markers Aps-1, yv, Mi, Cf-2/Cf-5, tl and pds. In order to incorporate the centromere into the integrated map, a radiation-induced deletion mapping strategy was applied, using irradiated pollen from L. pennellii LA716 in crosses to a L. esculentum line recessive for the markers yv and tl, that flank the centromere. Molecular analysis of the hemizygous yv-deletion and tl-deletion plants identified among the F1 progeny, provided an estimate of the size of the respective deletions and, thus, of the position of the centromere relative to the molecular markers linked to yv and tl. This radiation mapping approach also provided evidence showing that, unlike published data, the root knot nematode resistance gene Mi as well as the Cladosporium fulvum resistance genes Cf-2/Cf-5 are located on the short arm.