Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: Phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel

Contains fulltext : 98255.pdf (publisher's version ) (Open Access)BACKGROUND: Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. METHODS/DESIGN: The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE(100)C*6 versus FE(100)C*3 followed by Docetaxel(100)*3). DISCUSSION: In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE(100)C-Docetaxel(100), and 1,327 received French FE(100)C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up. TRIAL REGISTRATION: clinical Trials.gov NCT01222052

Gynecologists’ attitudes toward and use of complementary and integrative medicine approaches: results of a national survey in Germany

Abstract Purpose Despite patients’ widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals’ current implementation of it in clinical routine. A national survey was conducted to assess gynecologists’ attitudes to and implementation of complementary and integrative treatment approaches. Methods The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email. Results Questionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016). Conclusions There is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology

Lifestyle modifications after the diagnosis of gynecological cancer

Background!#!The influence of lifestyle factors on the quality of life, incidence and tumor recurrence has been evaluated in several studies and is gaining increasing importance in cancer research. However, the extent of the influence of such lifestyle factors on the quality of life of cancer patients remains largely unclear, as does the number of patients actually pursuing these lifestyle changes. The purpose of this study was to examine the prevalence and predictors of lifestyle changes in patients with gynecological cancer.!##!Methods!#!The survey consisted of a pseudonymous questionnaire that was conducted from January to May 2014 via a telephone interview with 141 patients with a gynaecological malignancy who had undergone surgery at our Department of Gynaecology and Obstetrics. Lifestyle factors (diet, physical activity, stress level, alcohol and nicotine consumption) prior to and after the diagnosis of cancer were evaluated.!##!Results!#!89% (n = 125) of the patients reported lifestyle changes after being diagnosed with cancer. There was a significant association between the implementation of lifestyle changes and age as well as the use of complementary medicine. Nutrition: 66% of the patients (n = 93) consumed more fruit and vegetables and 65% ate less meat (n = 92). Physical activity: 37% (n = 52) reported no change in their exercise routine, 36% (n = 51) described a decrease, 27% (n = 38) an increase in their physical activity. Subjective feeling of stress: 77% of the patients (n = 108) described a reduction in their perceived level of stress. Nicotine consumption: 63% (n = 12) of the 19 patients who were smokers at the time of the diagnosis quit or reduced smoking thereafter. Alcohol consumption: 47% (n = 61/129) of the patients reduced their alcohol consumption.!##!Conclusions!#!Most of the patients from our study group implemented lifestyle changes after being diagnosed with cancer. Prospective randomized trials are needed in order to determine the benefit of lifestyle changes (physical activity, dietary habits and stress reduction) for cancer survivors. The potential impact of lifestyle on the quality of life and the trajectory of the disease should be discussed with all oncological patients

Demand for integrative medicine among women in pregnancy and childbed: a German survey on patients’ needs

Abstract Background Although integrative medicine is gaining increasing attention and is claiming more and more its place in modern health care, it still plays a marginal role in conventional maternity care. The present study aims to examine the patterns of Complementary and Alternative Medicine (CAM) use and the demand for integrative therapies, including CAM, relaxation therapies, nutritional counseling, and psychological assistance, among women in pregnancy and childbed. Methods The survey was conducted from April 2017 to July 2017 by means of a pseudo-anonymous 38-item questionnaire at the Department of Gynecology and Obstetrics, Klinikum rechts der Isar, Technical University of Munich. Eligible participants were women hospitalized due to pregnancy related complications and women in childbed. Descriptive statistics were generated to determine patterns of CAM use and demand for integrative therapeutic approaches. Univariate analysis was used to detect associations between patients’ characteristics and their interest in the different integrative therapies. Furthermore, binary logistic regression was used to estimate the odds ratio of demand for CAM. Results A total of 394 out of 503 patients participated in the survey (78%). 60% declared using CAM in general, 45% specifically in relation to their pregnancy or childbed. Most commonly used modalities were vitamins (31% of all patients), yoga (24%), and herbal supplements (23%). Most popular sources of recommendation of CAM use were midwives and gynecologists. Integrative therapy options patients would have wanted alongside conventional maternity care were CAM (64%), relaxation therapies (44%), dietary counseling (28%), and psychological counseling (15%). Furthermore, associations between patients’ sociodemographic characteristics and their demand for integrative therapies were identified. Conclusions The results of this study demonstrate that there is a considerable demand for integrative medicine and widespread use of CAM among women during pregnancy and childbed in Germany. Maternity health care providers should be aware of these findings in order to be able to better address patients’ needs and wishes. Our study findings should be interpreted with regard to patients in an hospital setting

Demand for integrative medicine among women with breast and gynecological cancer: a multicenter cross-sectional study in Southern and Northern Germany

Purpose!#!The aim of this multicenter cross-sectional study was to analyze a cohort of breast (BC) and gynecological cancer (GC) patients regarding their interest in, perception of and demand for integrative therapeutic health approaches.!##!Methods!#!BC and GC patients were surveyed at their first integrative clinic visit using validated standardized questionnaires. Treatment goals and potential differences between the two groups were evaluated.!##!Results!#!340 patients (272 BC, 68 GC) participated in the study. The overall interest in IM was 95.3% and correlated with older age, recent chemotherapy, and higher education. A total of 89.4% were using integrative methods at the time of enrolment, primarily exercise therapy (57.5%), and vitamin supplementation (51.4%). The major short-term goal of the BC patients was a side-effects reduction of conventional therapy (70.4%); the major long-term goal was the delay of a potential tumor progression (69.3%). In the GC group, major short-term and long-term goals were slowing tumor progression (73.1% and 79.1%) and prolonging survival (70.1% and 80.6%). GC patients were significantly more impaired by the side-effects of conventional treatment than BC patients [pain (p = 0.006), obstipation (< 0.005)].!##!Conclusion!#!Our data demonstrate a high overall interest in and use of IM in BC and GC patients. This supports the need for specialized IM counseling and the implementation of integrative treatments into conventional oncological treatment regimes in both patient groups. Primary tumor site, cancer diagnosis, treatment phase, and side effects had a relevant impact on the demand for IM in our study population

Acute radiodermatitis in modern adjuvant 3D conformal radiotherapy for breast cancer - the impact of dose distribution and patient related factors

Abstract Purpose This study was performed to evaluate skin toxicity during modern three-dimensional conformal radiotherapy (3D-CRT) and to evaluate the importance of dose distribution and patient related factors. Material and methods This study comprises 255 patients with breast cancer treated with tangential three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery between 03/2012 and 05/2017. The median prescribed dose was 50.4 Gy (range 50–50.4) and 92.2% of the patients received a sequential boost of 10–16 Gy. Adverse skin toxicities (according to CTCAE v. 4.03 and the occurrence of moist desquamations) were assessed at the end of treatment. The dose distribution in the skin (5 mm strip from the patient outline) and in the CTV was evaluated and correlated to the CTCAE scores and the occurrence of moist desquamation. Results 42.4% of the patients developed grade I, 55.7% grade II and 2% grade III skin toxicities. Moist desquamation was observed in 59 cases (23.1%). Dose distribution within the CTV and skin was homogenous with only small areas receiving 107% of the prescribed dose (median: 0.7 cm3) in the CTV and 105% (median 0.5 cm3) in the skin. On univariate analysis breast size as well as V107%(CTV), V105%(skin) and V80%(skin) correlated significantly (p < 0.05) with the incidence of skin toxicity. On multivariate analysis only V80%(skin) was confirmed as independent risk factor. Conclusion Modern tangential multi-field 3D-CRT allows a homogeneous dose distribution with similar skin toxicity as compared to studies performing IMRT. Dose distribution within the skin (V80%) might have a relevant impact on the severity of skin toxicity and the occurrence of moist desquamation