Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal interval tumor reductive surgery for advanced ovarian cancer.

OBJECTIVES: Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. METHODS: In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). RESULTS: There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024-3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042-2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414-0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. CONCLUSIONS: IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

Pathologic and clinical tumor size discordance in early-stage cervical cancer: Does it matter?

OBJECTIVE: The objective of this study was to assess the rate of discordance between clinical and pathologic tumor size for women with stage IB1 cervical cancer (FIGO 2009 criteria), assess risk factors for discordance, and determine the impact of discordance on oncologic outcomes. METHODS: This was a secondary analysis of a prior multi-institutional retrospective review of patients diagnosed with stage IB1 (FIGO 2009 staging) cervical cancer undergoing radical hysterectomy between 2010 and 2017. Demographic, clinicopathologic, and oncologic data were collected. Pathologic upstaging was defined as having a preoperative diagnosis of stage IB1 cervical cancer with pathology demonstrating a tumor size >4 cm. Demographic and clinicopathologic data was compared using chi-square, fisher exact or 2-sided t-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Of the 630 patients, 77 (12%) were upstaged. Patients who were upstaged had lower rates of preoperative conization (p < .001) or preoperative tumor sizes ≤2 cm (p < .001). Upstaged patients had increased odds of deep stromal invasion, lymphovascular space invasion, positive margins and positive lymph nodes. Almost 88% of upstaged patients received adjuvant therapy compared to 29% of patients with tumors ≤4 cm (odds 18.49, 95% CI 8.99-37.94). Finally, pathologic upstaging was associated with an increased hazard of recurrence (hazard ratio [HR] 1.95, 95% CI 1.03-3.67) and all-cause death (HR 2.31, 95% CI 1.04-5.11). CONCLUSIONS: Pathologic upstaging in stage IB1 cervical cancer is relatively common. Upstaging is associated with an 18-fold increased risk of receipt of adjuvant therapy. Patients undergoing preoperative conization and those with tumors <2 cm had lower risks of upstaging. Improvement in preoperative assessment of tumor size may better inform primary treatment decisions.

Letrozole may be a valuable maintenance treatment in high-grade serous ovarian cancer patients.

OBJECTIVES: Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC). METHODS: We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n=8901) and HGSOC (n=527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n=4071). The same was performed in an independent cohort for matched primary and recurrent HGSOC (n=80). Finally, newly diagnosed ER+ HGSOC patients were offered a maintenance therapy with Letrozole. RESULTS: ESR1 was strongly expressed in similar levels in HGSOC as in breast cancer. We found a strong ER expression via IHC in both the primary and matched recurrent HGSOC, particularly in the Platinum-resistant subgroup. The additional use of Letrozole as maintenance treatment was associated with a significantly prolonged recurrence free interval (after 24months 60% when taking Letrozole versus 38.5% in the control group; p=0.035; RFS: IC50 reached by one subject versus 13.2months). This effect was also present in patients treated additionally with Bevacizumab; 20.8% of patients had no recurrence after 12months compared to 87.5% when taking Letrozole in addition to Bevacizumab (p=0.026). CONCLUSIONS: Primary HGSOC have a slightly higher ESR1 than and a similar ER expression breast cancer where aromatase inhibitor maintenance is routine for decades. Here we demonstrate evidence for the usefulness of Letrozole in HGSOC, particularly in patients with chemotherapy resistance or residual disease.

[Primary biliary cholangitis-established and novel therapies]. / Primär biliäre Cholangitis ­ etablierte und neue Therapien.

BACKGROUND: Patients with primary biliary cholangitis (PBC, formerly primary biliary cirrhosis) and insufficient treatment response or risk factors exhibit a remarkably increased risk for disease progression and associated complications. Furthermore, extrahepatic manifestations may considerably reduce quality of life in affected patients. OBJECTIVES: This article presents an overview on standard therapy with ursodeoxycholic acid (UDCA) and further therapeutic options in patients with insufficient treatment response. In addition, symptom-orientated therapies will be presented in a practical and compact way. METHODS: The current European and German guidelines from 2017 in addition to several research papers and expert opinions are the basis for this review. RESULTS: Every PBC patient should be treated with UDCA life-long. In case of insufficient response to UDCA, obeticholic acid (OCA) has been approved as second line therapy since 2016. Fibrates and budesonide present off-label options for certain patient subpopulations. Pruritus should initially be treated with colestyramine. In case of insufficient efficacy or intolerance, rifampicin represents the most effective off-label option. If fatigue is present, differential diagnoses shall be excluded and coping strategies combined with regular physical activity can have a positive effect. CONCLUSION: UDCA and OCA are effective and approved drugs for treating PBC. Patients with insufficient treatment response or risk factors have to be treated consequently. Due to the improved anti-cholestatic treatment options, therapies to reduce fatigue and pruritus are increasingly important.

Prospective study of successful autologous dendritic cell therapy in dogs with splenic stage II hemangiosarcoma.

Hemangiosarcoma is an aggressive tumour that most frequently occurs in larger, middle-aged dogs of certain breeds. The spleen is the most commonly affected organ. The aim of this prospective therapy study was to evaluate the clinical effect of autologous, monocyte-derived dendritic cell (DC) therapy in canine hemangiosarcoma stage II after splenectomy. Dogs (n=452) diagnosed with splenic hemangiosarcoma that underwent splenectomy were enrolled. Of these, 42 dogs with stage II entered the DC therapy study. The median survival time for the total group of 42 dogs was 203 days. The median survival for the group (n=34) that received the full DC therapy (≥3 vaccines) was 256 days, with a 29 % one-year survival rate and a hazard ratio of 0.30, adjusted to age and bodyweight (P=0.010). We further observed a significant increase in DC yield after each application and demonstrated that DC yield at the beginning of treatment is significantly related to patient survival. While further evidence is needed, we conclude that autologous, monocyte-derived DC therapy is a viable alternative to standard treatment methods of canine splenic stage II hemangiosarcoma.

Case report: 65-year-old man with metachronous left sided adrenal metastasis of hepatocellular carcinoma.

INTRODUCTION AND IMPORTANCE: Due to therapeutic advances and improvements in follow-up care, the diagnosis and treatment of extrahepatic metastases of hepatocellular carcinoma [HCC] have gained clinical significance. However, adrenal gland metastases of HCC remain a rare clinical encounter. Several systemic and local treatment options are discussed in current literature. Adrenalectomy in cases of isolated adrenal metastases with well-controlled intrahepatic lesions has been shown to benefit patients in case series. PRESENTATION OF THE CASE: This 65-year-old patient presented with suspected metachronous left sided adrenal metastasis seven years after bisegmentectomy for HCC and after undergoing trans-arterial chemoembolization [TACE] for multifocal intrahepatic recurrences while being listed for liver transplantation "beyond Milan criteria". Adrenalectomy was suggested for histopathological confirmation of the suspected metastasis and re-consideration for liver transplant. The resection was performed laparoscopically and metastasis of HCC was confirmed in histopathological analysis. Postoperatively, the patient recovered quickly. However, the patient decided against re-listing for liver transplantation. CLINICAL DISCUSSION: Current literature suggests, that minimally-invasive adrenalectomy should be considered in patients with no more than two extrahepatic lesions, a Child-Pugh-Score of less than A5, low alpha-fetoprotein [AFP] levels <100 ng/ml and size <3 cm. The oncological goal should be to achieve a tumor free extrahepatic situation with a potential oncological benefit. CONCLUSION: Our patient presented as an ideal candidate for resection of the adrenal gland metastasis and could have been re-assessed postoperatively for liver transplantation. Still, more research is needed to improve patient-selection for metastasectomy in HCC.

Determination and prospective validation of cut-off values for the diagnosis of liver cirrhosis for point shear-wave elastography/acoustic radiation force impulse imaging using the ACUSON Sequoia ultrasound system.

OBJECTIVES: Point shear-wave elastography (pSWE) alias acoustic radiation force impulse (ARFI) imaging is a well-established ultrasound-based technique for the non-invasive assessment of liver tissue stiffness. As cut-off values for liver cirrhosis cannot be transferred from one ultrasound system to another, this study aimed at determining cut-off values for the newly developed Siemens ACUSON Sequoia ultrasound system. METHODS: In a pilot study phase, two independent examiners conducted 10 pSWE measurements in an elasticity phantom and 32 healthy individuals for the determination of inter-examiner agreement. Afterwards, 22 cirrhotic patients and 57 patients with chronic liver disease undergoing liver biopsy underwent pSWE. Patient characteristics and stiffness values were compared for individuals with and without liver cirrhosis. Diagnostic accuracies of cut-off values for the diagnosis of liver cirrhosis were calculated using areas under the receiver operating characteristics analysis and Youden's index. In a subsequent validation study phase, these cut-off values were validated prospectively in 107 cirrhotic and 68 non-cirrhotic patients. RESULTS: Inter-examiner agreement was excellent for measurements in the elasticity phantom (intra-class correlation coefficient [ICC] = 0.998; P  < 0.001), and good for measurements in patients (ICC = 0.844; P  < 0.001). The best cut-off value for the diagnosis of liver cirrhosis was 1.405 m/s with an AUC of 0.872, a sensitivity of 88.2% and a specificity of 88.2% ( P  < 0.001). CONCLUSION: ARFI elastography using the Siemens ACUSON Sequoia showed a good inter-examiner agreement. The optimal cut-off value was lower than the cut-off values described for former generations of ultrasound devices. These preliminary results should be confirmed in larger patient collectives with histology as the reference standard.

Flagellin perception varies quantitatively in Arabidopsis thaliana and its relatives.

Much is known about the evolution of plant immunity components directed against specific pathogen strains: They show pervasive functional variation and have the potential to coevolve with pathogen populations. However, plants are effectively protected against most microbes by generalist immunity components that detect conserved pathogen-associated molecular patterns (PAMPs) and control the onset of PAMP-triggered immunity. In Arabidopsis thaliana, the receptor kinase flagellin sensing 2 (FLS2) confers recognition of bacterial flagellin (flg22) and activates a manifold defense response. To decipher the evolution of this system, we performed functional assays across a large set of A. thaliana genotypes and Brassicaceae relatives. We reveal extensive variation in flg22 perception, most of which results from changes in protein abundance. The observed variation correlates with both the severity of elicited defense responses and bacterial proliferation. We analyzed nucleotide variation segregating at FLS2 in A. thaliana and detected a pattern of variation suggestive of the rapid fixation of a novel adaptive allele. However, our study also shows that evolution at the receptor locus alone does not explain the evolution of flagellin perception; instead, components common to pathways downstream of PAMP perception likely contribute to the observed quantitative variation. Within and among close relatives, PAMP perception evolves quantitatively, which contrasts with the changes in recognition typically associated with the evolution of R genes.

Effect of lifestyle intervention on cardiometabolic risk factors: results of the POWER-UP trial.

OBJECTIVE: To investigate the effects of three weight loss interventions on cardiometabolic risk factors, including blood pressure, lipids, glucose and markers of insulin resistance and inflammation. We also examined whether categories of incremental weight change conferred greater improvements on these parameters. METHODS: This 2-year trial was conducted in a primary care setting and included 390 obese participants who were randomly assigned to one of three interventions: (1) Usual Care (quarterly primary care provider (PCP) visits that included education about weight management); (2) Brief Lifestyle Counseling (quarterly PCP visits plus monthly behavioral counseling provided by a trained auxiliary health-care provider); or (3) Enhanced Brief Lifestyle Counseling (the same care as described for the previous intervention, plus weight loss medications or meal replacements). The primary outcome was change in cardiometabolic risk factors among groups. RESULTS: At month 24, participants in Enhanced Brief Lifestyle Counseling lost significantly more weight than those in Usual Care (4.6 vs 1.7 kg), with no other significant differences between groups. Enhanced Brief Lifestyle Counseling produced significantly greater improvements in high-density lipoprotein (HDL) cholesterol and triglyceride levels at one or more assessments, compared with the other two interventions. Markers of insulin resistance also improved significantly more in this group throughout the 2 years. Collapsing across the three groups, greater weight loss was associated with greater improvements in triglycerides, HDL cholesterol and markers of insulin resistance and inflammation at month 24, but was not significantly associated with reductions in blood pressure, total cholesterol and low-density lipoprotein cholesterol at any time. CONCLUSIONS: Enhanced Brief Lifestyle Counseling, which produced the largest weight loss, was generally associated with the greatest improvements in cardiovascular risk factors. These findings suggest that an intensive weight loss intervention, delivered in a primary care setting, can help obese individuals improve some cardiometabolic risk factors.

The impact of a primary care-based weight loss intervention on the quality of life.

OBJECTIVE: This study investigated changes in the quality of life of men and women who participated in a primary care-based weight loss intervention program. METHODS: Participants were enrolled in a 2-year randomized clinical trial (POWER-UP) conducted at the University of Pennsylvania and in six affiliated primary care practices. Inclusion criteria included the presence of obesity (body mass index of 30-50 kg m(-2)) and at least two components of the metabolic syndrome. MAIN OUTCOME MEASURES: Quality of life was assessed by three measures: the Short Form Health Survey (SF-12); the Impact of Weight on Quality of Life-Lite; and the EuroQol-5D. RESULTS: Six months after the onset of treatment, and with a mean weight loss of 3.9 ± 0.3 kg, participants reported significant improvements on all measures of interest with the exception of the Mental Component Score of the SF-12. These changes remained significantly improved from baseline to month 24, with the exception of the EuroQol-5D. Many of these improvements were correlated with the magnitude of weight loss and, for the most part, were consistent across gender and ethnic group. CONCLUSIONS: Individuals with obesity and components of the metabolic syndrome reported significant improvements in most domains of the quality of life with a modest weight loss of 3.7% of initial weight, which was achieved within the first 6 months of treatment. The majority of these improvements were maintained at month 24, when participants had lost 3.0% of their weight.

Managing obesity in primary care practice: an overview with perspective from the POWER-UP study.

Primary care practitioners (PCPs) have been encouraged to screen all adults for obesity and to offer behavioral weight loss counseling to the affected individuals. However, there is limited research and guidance on how to provide such intervention in primary care settings. This led the National Heart, Lung and Blood Institute in 2005 to issue a request for applications to investigate the management of obesity in routine clinical care. Three institutions were funded under a cooperative agreement to undertake the practice-based opportunities for weight reduction (POWER) trials. The present article reviews selected randomized controlled trials, published before the initiation of POWER, and then provides a detailed overview of the rationale, methods and results of the POWER trial conducted at the University of Pennsylvania (POWER-UP). POWER-UP's findings are briefly compared with those from the two other POWER trials, conducted at Johns Hopkins University and Harvard University/Washington University. The methods of delivering behavioral weight loss counseling differed markedly across the three trials, as captured by an algorithm presented in the article. Delivery methods ranged from having medical assistants and PCPs from the practices provide counseling to using a commercially available call center, coordinated with an interactive website. Evaluation of the efficacy of primary care-based weight loss interventions must be considered in light of costs, as discussed in relation to the recent treatment model proposed by the Centers for Medicare and Medicaid Services.

Gender differences in the relationship between symptoms of depression and high-sensitivity CRP.

BACKGROUND: Depression has been associated with increased risk of cardiovascular disease. The inflammatory marker C-reactive protein (CRP) has also been identified as an independent predictor of short- and long-term cardiovascular disease events. Inflammation may influence the relationship between depression and cardiovascular disease. OBJECTIVE: The objective of this study was to investigate the association between symptoms of depression and high-sensitivity CRP (hs-CRP) in an obese clinical population. We also sought to determine whether this relationship was different in men and women, given prior reports of a gender effect. METHODS: Symptoms of depression and hs-CRP were measured in 390 participants enrolled in a weight loss intervention trial that was delivered in a primary care setting. Symptoms of depression were evaluated with the Patient Health Questionnaire-8 (PHQ-8), in which a score ≥ 10 is consistent with major depression. RESULTS: A total of 58 (15.2%) participants reported a PHQ-8 score ≥ 10. The median (interquartile range) hs-CRP concentration was significantly higher in participants with symptoms consistent with major depression (7.7 (4.2-13) mg l(-1)) compared with those without depression (5.1 (3-9.7) mg l(-1); P<0.01). Symptoms consistent with major depression were significantly associated with log-transformed hs-CRP concentrations in an analysis adjusted for age, gender, obesity class and other metabolic variables (P=0.04). When interaction by gender was examined, this relationship remained significant in men (P<0.01) but not in women (P=0.32). CONCLUSIONS: Symptoms consistent with major depression were significantly associated with hs-CRP in men only, even after adjusting for age, obesity class, metabolic variables and medications known to affect inflammation. This finding suggests that there are biologic differences between men and women that may modify the relationship between hs-CRP and depression. Further studies are needed to elucidate the biologic basis for these findings.

Changes in eating, physical activity and related behaviors in a primary care-based weight loss intervention.

OBJECTIVE: To examine changes in eating behaviors and physical activity, as well as predictors of weight loss success, in obese adults who participated in a 2-year behavioral weight loss intervention conducted in a primary care setting. DESIGN: A longitudinal, randomized controlled, multisite trial. SUBJECTS: Three hundred ninety obese (body mass index, 30-50 kg m(-2)) adults, ≥ 21 years, in the Philadelphia region. METHODS: Participants were assigned to one of three interventions: (1) Usual Care (quarterly primary care provider (PCP) visits that included education on diet and exercise); (2) Brief Lifestyle Counseling (quarterly PCP visits plus monthly lifestyle counseling (LC) sessions about behavioral weight control); or (3) Enhanced Brief LC (the previous intervention with a choice of meal replacements or weight loss medication). RESULTS: At month 24, participants in both Brief LC and Enhanced Brief LC reported significantly greater improvements in mean (± s.e.) dietary restraint than those in Usual Care (4.4 ± 0.5, 4.8 ± 0.5 and 2.8 ± 0.5, respectively; both P-values ≤ 0.016). The percentage of calories from fat, along with fruit and vegetable consumption, did not differ significantly among the three groups. At month 24, both the Brief LC and Enhanced Brief LC groups reported significantly greater increases than usual care in energy expenditure (kcal per week) from moderately vigorous activity (+593.4 ± 175.9, +415.4 ± 179.6 and -70.4 ± 185.5 kcal per week, respectively; both P-values ≤ 0.037). The strongest predictor of weight loss at month 6 (partial R(2)=33.4%, P<0.0001) and at month 24 (partial R(2)=19.3%, P<0.001) was food records completed during the first 6 months. Participants who achieved a 5% weight loss at month 6 had 4.7 times greater odds of maintaining a ≥ 5% weight loss at month 24. CONCLUSIONS: A behavioral weight loss intervention delivered in a primary care setting can result in significant weight loss, with corresponding improvements in eating restraint and energy expenditure. Moreover, completion of food records, along with weight loss at month 6, is a strong predictor of long-term weight loss.

Cost-effectiveness of a primary care intervention to treat obesity.

BACKGROUND: Data on the cost-effectiveness of the behavioral treatment of obesity are not conclusive. The cost-effectiveness of treatment in primary care settings is particularly relevant. METHODS: We conducted a within-trial cost-effectiveness analysis of a primary care-based obesity intervention. Study participants were randomized to: Usual Care (UC; quarterly visits with their primary care provider); Brief Lifestyle Counseling (BLC; quarterly provider visits plus monthly weight loss counseling visits) or Enhanced Brief Lifestyle Counseling (EBLC; all above interventions, plus choice of meal replacements or weight loss medication). A health-care payer perspective was used. Intervention costs were estimated from tracking data obtained prospectively. Quality-adjusted life years (QALYs) were estimated with the EuroQol-5D. We estimated cost per kilogram-year of weight loss and cost per QALY. RESULTS: Weight losses after 2 years were 1.7, 2.9 and 4.6 kg for UC, BLC and EBLC, respectively (P=0.003 for comparison of EBLC vs UC). The incremental cost per kilogram-year lost was $292 for EBLC compared with UC (95% confidence interval (CI): $219-$437). The short-term incremental cost per QALY was $115,397, but the 95% CI were undefined. Comparison of short-term cost per kg with published estimates of longer-term cost per QALY suggested that the intervention could be cost-effective over the long term (≥ 10 years). CONCLUSIONS: A primary care intervention that includes monthly counseling visits and a choice of meal replacements or weight loss medication could be a cost-effective treatment for obesity over the long term. However, additional studies are needed on the cost-effectiveness of behavioral treatment of obesity.

Pegylated liposomal doxorubicin (PLD) in daily practice-A single center experience of treatment with PLD in patients with comorbidities and older patients with metastatic breast cancer.

PURPOSE: Real-world data about pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) are limited. We have aimed to highlight the role of PLD in daily practice focusing on older patients and patients with comorbidities with MBC. METHODS: We analyzed electronic records of all patients with advanced/metastatic breast cancer treated with single-agent PLD at the University Hospital Basel between 2003 and 2021. Primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). We performed univariate and multivariate analysis for clinical variables. RESULTS: 112 patients with MBC having received single-agent PLD in any treatment line were analyzed, including 34 patient who were older than 70 years and 61 patients with relevant comorbidities. Median TTNC, OS, and PFS for treatment with PLD were 4.6, 11.9, and 4.4 months, respectively. ORR was 13.6%. Age >70 years predicted shorter OS (median 11.2 months) in multivariate analysis (hazard ratio [HR] 1.83, 95% CI 1.07-3.11, p = 0.026). Age and comorbidities did not significantly affect other endpoints. Unexpectedly, hypertension predicted longer TTNC (8.3 months, p = 0.04) in univariate analysis, maintained in multivariate analysis as a trend for both TTNC (HR 0.62, p = 0.07) and OS (HR 0.63, p = 0.1). CONCLUSION: Age predicted shorter OS significantly but median OS was not relevantly shorter in older patients. PLD remains a treatment option in patients with comorbidities and older patients with MBC. However, our real-world results of PLD appear underwhelming compared to relevant phase II trials through all age groups, pointing to an efficacy-effectiveness gap, possibly due to sampling bias.

Clinical application of the 21-gene oncotype recurrence score in an older cohort: A single center experience.

BACKGROUND: In early luminal breast cancer, the Oncotype DX® Recurrence Score (RS) prognostic and predictive value with regards to chemotherapy (CHT) application benefit has been broadly validated. In older patients its value has not been deeply addressed. This study aimed to evaluate the benefits of RS testing and to look at differences in treatment allocation for these patients when compared with younger ones. METHODS: We included data from consecutive patients with early luminal HER2-negative breast cancer, treated between 2010 and 2022 at the University Hospital Basel and Cantonal Hospital Baselland, Switzerland. The older cohort included 63 (19%) patients aged ≥70, and the younger cohort 263 (81%) patients aged <70. RESULTS: Older breast cancer patients had more co-morbidities (N = 36, 57% vs. N = 92, 35%, p = 0.002) and a higher clinical risk status (N = 49, 78% vs. N = 155, 59%; p = 0.01) when compared to younger patients. Histopathologic characteristics were significantly different between the two cohorts. Although older patients had a higher clinical risk status (78% vs. 59%) (p = 0.01), most of them (74%) received no CHT. Specifically, adjuvant CHT was administered less frequently in older than in younger patients (13% vs. 22%; p = 0.01). Moreover, older patients were less likely to complete CHT (>4 cycles: 78% vs. 97%). CONCLUSION: Breast cancer patients aged ≥70 have higher clinical risk status, more co-morbidities, higher clinical stage (driven by larger tumor size), and more often RS ≥26. However, they receive fewer adjuvant RT and CHT than those aged <70. RS maintains its independent prognostic value in older patients. However, assessing the predictive value of additional CHT benefit remains challenging due to significant differences in CHT administration. Although therapy decision-making in older patients with breast cancer still follows RS-based guidelines, clinical practice indicates an individualized treatment approach.

The accuracy of BI-RADS classification of breast ultrasound as a first-line imaging method.

PURPOSE: The aim was to evaluate the accuracy of BI-RADS categories 3 - 5 in breast ultrasound (US) as the first-line imaging method. MATERIALS AND METHODS: 5077 examinations of a consecutive, unselected and mixed collective of symptomatic and asymptomatic patients were performed. Of these examinations, 835 cases of BIRADS 3 - 5 could be analyzed. RESULTS: The PPV with respect to a malignant lesion for BI-RADS 3, 4, 5 was 0.03, 0.48, and 0.97, respectively. When BI-RADS 4 and 5 cases are considered to be suspicious, the ratio of benign to malignant findings corresponds to 1:1.8. Analyzing BIRADS 3 - 5 lesions, the sensitivity, specificity and accuracy are 0.92, 0.85, and 0.87, respectively. CONCLUSION: The data support the feasibility of US for discriminating malignant from benign findings corresponding to the ACR BI-RADS classification without excessively increasing the number of unnecessary biopsies.

[Breast cancer - Treatment guidelines and new treatment options in 2012, a medical oncology prospective]. / Das Mammakarzinom - Therapiestandards und neue Therapiemöglichkeiten 2012, ein onkologisches Review.

Breast cancer is the leading cancer in women with an annual incidence rate of 110/100.000 women in all age groups in Europe. The incidence rate increases in older women. Treatment includes surgery, radiotherapy, chemotherapy with or without antibody therapy and hormonal treatment. During the last 40 years the survival rate has significantly improved. From the 1970ies to 2010 the five year survival rate has risen from 85% to 98% early breast cancer. Similarly, in metastatic breast cancer 5-year survival has increased from below 10% in 1970 to 26% in 2010. This was possible because of better treatment options and better screening causing earlier diagnosis of breast cancer. This article reviews the standard treatment of breast cancer according to ESMO/ASCO guidelines and discusses new treatment options and new therapeutic strategies for breast cancer.

Relation of health-related quality of life to metabolic syndrome, obesity, depression and comorbid illnesses.

BACKGROUND: Metabolic syndrome has been associated with impaired health-related quality of life (HRQoL) in several studies. Many studies used only one HRQoL measure and failed to adjust for important confounding variables, including obesity, depression and comorbid conditions. OBJECTIVE: To investigate the relationship between metabolic syndrome and HRQoL using multiple measures. We also sought to determine whether increasing body mass index or diabetes status further modified this relationship. METHODS: This cross-sectional study included 390 obese participants with elevated waist circumference and at least one other criterion for metabolic syndrome. Of these 390 participants, 269 had metabolic syndrome (that is, they met 3 out of the 5 criteria specified by the NCEP (National Cholesterol Education Program)) and 121 did not. Participants were enrolled in a primary care-based weight-reduction trial. HRQoL was assessed using two generic instruments, the Medical Outcomes Study Short-Form 12 and the EuroQol-5D, as well as an obesity-specific measure, the Impact of Weight on Quality of Life. Differences in HRQoL were compared among participants with and without metabolic syndrome. Multivariable linear regression was used to determine how HRQoL varied according to metabolic syndrome status, and whether factors including weight, depression and burden of comorbid disease modified this relationship. RESULTS: Metabolic syndrome was not associated with HRQoL as assessed by any of the measures. In univariable analysis, depression, disease burden and employment status were significantly associated with worse HRQoL on all instruments. In multivariable models, only depression remained significantly associated with reduced HRQoL on all measures. Increasing obesity and diabetes status did not modify the relationship between metabolic syndrome and HRQoL. CONCLUSION: In contrast to previous studies, metabolic syndrome was not associated with impaired HRQoL as assessed by multiple measures. This suggests that metabolic syndrome in itself is not associated with decreased HRQoL, but other factors such as obesity, depression and greater disease burden may significantly influence the quality of life in this population.