Preoperative staging by multimodal imaging in newly diagnosed breast cancer: Diagnostic performance of contrast-enhanced spectral mammography compared to conventional mammography, ultrasound, and MRI.

PURPOSE: To compare contrast-enhanced spectral mammography (CESM) with mammography (Mx), ultrasound (US), and magnetic resonance imaging (MRI) regarding breast cancer detection rate and preoperative local staging. MATERIAL AND METHODS: This prospective observational, single-centre study included 128 female patients (mean age 55.8 ± 11.5 years) with a newly diagnosed malignant breast tumour during routine US and Mx were prospectively enrolled. CESM and MRI examinations were performed within the study. Analysis included interreader agreement, tumour type and grade distribution, detection rates (DR), imaging morphology, contrast-enhancement and was performed by two independent readers blinded to patient history and histopathological diagnosis. Assessment of local disease extent was compared between modalities via Bland-Altman plots. RESULTS: One-hundred-and-ten tumours were classified as NST (85.9%), 4 as ILC (3.1%) and 10 as DCIS (7.8%). DR was highest for MRI (128/128, 100.0%), followed by US (124/128, 96.9%) and CESM (123/128, 96.1%) and lowest for conventional Mx (106/128, 82.8%) (p = 0.0002). Higher breast density did not negatively affect DR of US, CESM or MRI. Local tumour extent measurements based on CESM (Bland-Altman bias 6.6, standard deviation 30.2) showed comparable estimation results to MRI, surpassing Mx (23.4/43.7) and US (35.4/40.5). Even though detection of multifocality and multicentricity was highest for CESM and MRI (p < 0.0001), second-look rates, i.e., targeted US examinations after MRI or CESM, were significantly lower for CESM (10.2% of cases) compared to MRI (16.2%) with a significantly higher true positive rate for CESM (72.0%) vs. MRI (42.5%). CONCLUSION: CESM is a viable alternative to MRI for lesion detection and local staging in newly diagnosed malignant breast cancer and provides higher specificity in regard to second-look examinations.

Real-world experience with anti-PD-1/PD-L1 monotherapy in patients with non-small cell lung cancer : A retrospective Austrian multicenter study.

OBJECTIVE: As real-world data regarding immunotherapy for non-small cell lung cancer are lacking for Austria, we conducted a retrospective study in six hospitals to present data from real-world practice. METHODS: Patients with metastatic non-small cell lung cancer were stratified into two groups, either patients with first-line pembrolizumab monotherapy (cohort 1) or patients with second-line nivolumab, pembrolizumab or atezolizumab monotherapy (cohort 2). Primary outcome measures were objective response rate and overall survival. A matched-pair analysis was performed to compare overall survival to patients from the Tyrolean Lung Cancer Project as a historical control group. RESULTS: In total, 89 patients were identified, 42 patients in cohort 1 and 47 patients in cohort 2. The objective response rates were 43.3% and 31.4%, respectively. The median overall survival was 17.0 months (95% CI 11.7-21.5 months) in cohort 1 and 18.7 months (95% CI 9.5-23.4 months) in cohort 2. Treatment-related adverse events grades 3 and 4 were reported in 11.2% of patients. The matched-pair analysis showed a median overall survival of 15.2 months (95% CI 7.6-20.4 months) for first-line pembrolizumab monotherapy compared to 9.8 months (95% CI 7.8-11.6 months) for the historical control (p = 0.43). In cohort 2, a median overall survival of 20.3 months (95% CI 6.9-26.2 months) for second-line immunotherapy compared to 5.4 months (95% CI 3.2-11.7 months) for the historical control (p = 0.18) was shown. CONCLUSION: The results are comparable with other real-world studies and, when matched to historical controls, support the improvement in outcomes made possible by these agents.

Comparative Effectiveness and Safety of Allografts and Autografts in Posterior Cruciate Ligament Reconstruction Surgery: A Systematic Review.

PURPOSE: To evaluate the evidence of the effectiveness and safety of allografts compared to autografts in posterior cruciate ligament reconstruction. METHODS: Four electronic databases were systematically searched for eligible randomized controlled studies. Crucial effectiveness outcomes included patient-reported function, activity level and symptoms, clinical knee stability, health-related quality of life, and patient satisfaction. Safety was evaluated through graft failures, revisions, reruptures and complications. The internal validity of the studies was assessed by the Cochrane risk of bias tool, and the strength of the evidence was judged according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Two randomized controlled studies were included: 50 patients were analyzed in the allograft group and 58 in the autograft group. No statistically significant postoperative differences were reported between the groups for patient-reported function, activity levels or symptoms. One study reported a statistically significant difference in instrumented postoperative anteroposterior knee laxity favoring stability in autografts. This difference is, however, not relevant in the clinical setting. Insufficient evidence was found to judge safety outcomes and because complications were poorly measured, and none of the studies reported on graft failure, revision or rerupture rates. The studies were judged with unclear to high risk of bias. The strength of the evidence for effectiveness and safety was judged to be low to very low, according to GRADE. CONCLUSIONS: Allografts may be comparable to autografts for crucial effectiveness outcomes, but insufficient evidence was found to judge crucial safety outcomes due to poor reporting of safety measures and outcomes. Results should be interpreted with caution because there is lack of good-quality evidence to support the superiority of allografts over autografts due to the high risk of bias in the primary studies and overall very low strength of the body of evidence according to GRADE. LEVEL OF EVIDENCE: Systematic review of Level II studies.

Algorithms to identify COPD in health systems with and without access to ICD coding: a systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality worldwide. Estimation of incidence, prevalence and disease burden through routine insurance data is challenging because of under-diagnosis and under-treatment, particularly for early stage disease in health care systems where outpatient International Classification of Diseases (ICD) diagnoses are not collected. This poses the question of which criteria are commonly applied to identify COPD patients in claims datasets in the absence of ICD diagnoses, and which information can be used as a substitute. The aim of this systematic review is to summarize previously reported methodological approaches for the identification of COPD patients through routine data and to compile potential criteria for the identification of COPD patients if ICD codes are not available. METHODS: A systematic literature review was performed in Medline via PubMed and Google Scholar from January 2000 through October 2018, followed by a manual review of the included studies by at least two independent raters. Study characteristics and all identifying criteria used in the studies were systematically extracted from the publications, categorized, and compiled in evidence tables. RESULTS: In total, the systematic search yielded 151 publications. After title and abstract screening, 38 publications were included into the systematic assessment. In these studies, the most frequently used (22/38) criteria set to identify COPD patients included ICD codes, hospitalization, and ambulatory visits. Only four out of 38 studies used methods other than ICD coding. In a significant proportion of studies, the age range of the target population (33/38) and hospitalization (30/38) were provided. Ambulatory data were included in 24, physician claims in 22, and pharmaceutical data in 18 studies. Only five studies used spirometry, two used surgery and one used oxygen therapy. CONCLUSIONS: A variety of different criteria is used for the identification of COPD from routine data. The most promising criteria set in data environments where ambulatory diagnosis codes are lacking is the consideration of additional illness-related information with special attention to pharmacotherapy data. Further health services research should focus on the application of more systematic internal and/or external validation approaches.

Combined screening with mammography and ultrasound in a population-based screening program.

OBJECTIVES: To compare the performance of screening with mammography combined with ultrasound versus mammography alone in women at average risk for breast cancer. METHODS: 66,680 women underwent physician-performed ultrasound as an adjunct to screening mammography. Histological results and follow-up at one year were used as reference standard for sensitivity. Main outcome measures were cancer detection rate, sensitivity, recall rate, biopsy rate, and positive predictive value of biopsy for combined screening with mammography plus ultrasound versus mammography alone. RESULTS: The overall sensitivity of mammography only was 61.5% in women with dense breasts and 86.6% in women with non-dense breasts. The sensitivity of mammography plus ultrasound combined was 81.3% in women with dense breasts and 95.0% in women with non-dense breasts. Adjunctive ultrasound increased the recall rate from 10.5 to 16.5 per 1000 women screened, and increased the biopsy rate from 6.3 to 9.3 per 1000 women screened. The positive predictive value of biopsy was 55.5% (95% CI 50.6%-60.3%) for mammography alone and 43.3 (95% CI 39.4%-47.3%) for combined mammography plus ultrasound. CONCLUSIONS: Supplemental ultrasound improves cancer detection in screening of women at average risk for breast cancer. Recall rates and biopsy rates can be kept within acceptable limits.

Performance of 4 years of population-based mammography screening for breast cancer combined with ultrasound in Tyrol / Austria.

BACKGROUND: Systems for the delivery of screening mammography vary among countries and these differences can influence screening effectiveness. We evaluated the performance of organized mammography screening for breast cancer combined with ultrasound in Tyrol / Austria, an approach that differs from many other population-based screening programs. METHODS: Data on women aged 40-69 years screened in the period from June 2008 to May 2012 were collected within the framework of an organized screening program. A total of 272,555 invitations were sent to the target population living in Tyrol and 176,957 screening examinations were performed. We analyzed the main performance indicators as defined by European Union (EU) guidelines and some important estimates of harms. RESULTS: The estimated 2­year participation rate was 56.9%. As ultrasound is implemented as second-line screening procedure, 76.2% of all women screened underwent supplementary ultrasound. In total 2322 women were recalled for further assessment (13.1 per 1000 screens) and 1351 biopsies were performed (7.6 per 1000 screens). The positive predictive value was 28.2% for assessment and 48.5% for biopsies. The cancer detection rate was 3.7 per 1000 screens and the proportion of all stage II+ screen-detected cancers was 35.5%. The interval cancer rate was 0.33 and 0.47 per 1000 screens in the first and second years, respectively. The estimated cumulative risk for a false positive screening result and an unnecessary biopsy for women following the invitation approach was 21.1% and 9.4%, respectively. CONCLUSION: The performance of our population-based screening approach combining mammography and ultrasound is very favorable and potential harm is kept very low compared to other European mammography screening programs for breast cancer.

Reduction in advanced breast cancer after introduction of a mammography screening program in Tyrol/Austria.

BACKGROUND: We analysed all female breast cancer (BC) cases in Tyrol/Austria regarding the shift in cancer characteristics, especially the shift in advanced BC, for the group exposed to screening as compared to the group unexposed to screening. METHODS: The analysis was based on all BC cases diagnosed in women aged 40-69 years, resident in Tyrol, and diagnosed between 2009 and 2013. The data were linked to the Tyrolean mammography screening programme database to classify BC cases as "exposed to screening" or "unexposed to screening". Age-adjusted relative risks (RR) were estimated by relating the exposed to the unexposed group. RESULTS: In a total of about 145,000 women aged 40-69 years living in Tyrol during the study period, 1475 invasive BC cases were registered. We estimated an age-adjusted relative risk (RR) for tumour size ≥ 21 mm of 0.72 (95% confidence interval (CI) 0.60 to 0.86), for metastatic BC of 0.27 (95% CI 0.17 to 0.46) and for advanced BC of 0.83 (95% CI 0.71 to 0.96), each comparing those exposed to those unexposed to screening, respectively. CONCLUSION: In our population-based registry analysis we observed that participation in the mammography screening programme in Tyrol is associated with a 28% decrease in risk for BC cases with tumour size ≥ 21 mm and a 17% decrease in risk for advanced BC. We therefore expect the Tyrolean mammography programme to show a reduction in BC mortality.

Patient-reported urinary incontinence and erectile dysfunction following radical prostatectomy: results from the European Prostate Centre Innsbruck.

INTRODUCTION: Urinary and erectile functions were assessed by using self-administered validated questionnaires in patients undergoing radical prostatectomy. MATERIALS AND METHODS: In a prospective observational study, a total of 253 consecutive patients diagnosed with clinically localised prostate cancer between 2008 and 2009 at the European Prostate Centre Innsbruck were included. Patient-reported outcomes were assessed before radical prostatectomy and 12 months postoperatively using the validated International Consultation on Incontinence Questionnaire (ICIQ) and the International Index of Erectile Function (IIEF). The Wilcoxon signed-rank test and Chi square statistics were used for analysis. RESULTS: The study showed that before radical prostatectomy, urinary incontinence of various severity grades was reported in 18.8, postoperatively in 63.0% (p < 0.001) and erectile dysfunction of various degrees was reported in 39.6 at baseline compared to 80.1% 12 months postoperatively (p < 0.001). CONCLUSIONS: This study suggests that radical prostatectomy is associated with a significantly increased risk of urinary incontinence and erectile dysfunction 12 months postoperatively.

Prediction of cancer incidence in Tyrol/Austria for year of diagnosis 2020.

BACKGROUND: Prediction of the number of incident cancer cases is very relevant for health planning purposes and allocation of resources. The shift towards elder age groups in central European populations in the next decades is likely to contribute to an increase in cancer incidence for many cancer sites. In Tyrol, cancer incidence data have been registered on a high level of completeness for more than 20 years. We therefore aimed to compute well-founded predictions of cancer incidence for Tyrol for the year 2020 for all frequent cancer sites and for all cancer sites combined. METHODS: After defining a prediction base range for every cancer site, we extrapolated the age-specific time trends in the prediction base range following a linear model for increasing and a log-linear model for decreasing time trends. The extrapolated time trends were evaluated for the year 2020 applying population figures supplied by Statistics Austria. RESULTS: Compared with the number of annual incident cases for the year 2009 for all cancer sites combined except non-melanoma skin cancer, we predicted an increase of 235 (15 %) and 362 (21 %) for females and males, respectively. For both sexes, more than 90 % of the increase is attributable to the shift toward older age groups in the next decade. The biggest increase in absolute numbers is seen for females in breast cancer (92, 21 %), lung cancer (64, 52 %), colorectal cancer (40, 24 %), melanoma (38, 30 %) and the haematopoietic system (37, 35 %) and for males in prostate cancer (105, 25 %), colorectal cancer (91, 45 %), the haematopoietic system (71, 55 %), bladder cancer (69, 100 %) and melanoma (64, 52 %). CONCLUSIONS: The increase in the number of incident cancer cases of 15 % in females and 21 % in males in the next decade is very relevant for planning purposes. However, external factors cause uncertainty in the prediction of some cancer sites (mainly prostate cancer and colorectal cancer) and the prediction intervals are still broad. Therefore, our predictions must be interpreted with some caution.

Increased suicide risk in cancer patients in Tyrol/Austria.

OBJECTIVES: To investigate whether suicide risk in Tyrol/Austria was increased for cancer patients as compared to the general population and whether subgroups at excess risk could be defined. STUDY DESIGN AND SETTING: Cohort design based on all malignant cancer cases diagnosed in Tyrol between 1991 and 2010 and excluding nonmelanoma skin cancer. Entry date was date of diagnosis of the index cancer; exit date was either date of suicide or date of death for reasons other than suicide or end of follow-up (Dec 31, 2011). Standardized mortality ratios (SMRs) were computed in the classical way after adjustment for sex, age and year of follow-up. RESULTS: For all cancer sites except nonmelanoma skin cancer, we observed a SMR of 1.86 [95% confidence interval (CI), 1.57-2.19]. Suicide risk was greatest during the first 6 months after diagnosis with an SMR of 4.74 (95% CI, 3.27-6.66) and was more than fivefold in cases with advanced Stage IV. We observed the greatest excess risk for suicide in patients with head and neck cancers (13 suicides; SMR, 4.73; 95% CI, 2.52-8.09) and lung cancer (14 suicides; SMR, 4.16; 95% CI, 2.27-6.98). CONCLUSION: In our study population in Tyrol/Austria, we observed a twofold suicide risk in cancer patients as compared with the general population, with the excess risk concentrated in the period shortly after diagnosis and in patients with poor prognosis. Therefore, psychooncological care should be intensified in this group of patients.

Scanning the horizon: development and implementation of an early awareness system for anticancer drugs in Austria.

BACKGROUND: Due to increasing expenditures for cancer therapies, an instrument was needed in Austria to facilitate the evidence-based use of new anticancer drugs and to pre-estimate their financial implications. OBJECTIVES: To describe and analyse the development and implementation of a Horizon Scanning System (HSS) in Austria that allows for the evaluation of new anticancer drugs before their routine introduction into clinical practice in order to inform decision-makers. METHODS: Common stages involved in HSSs were identified by a literature review and in cooperation with experts. A first concept for an HSS in Oncology was developed and piloted, and further adjustments were made after several feedback rounds with experts in oncology. RESULTS: To specifically tailor the five common stages of HSSs to the needs of our HSS, a continually evolving process was required. Now, 21 information sources are regularly scanned, the information is retrieved and extracted in a standardised format, and only anticancer drugs in phase III are included and prioritised by a team of eight experts. Since the HSS in Oncology was implemented as a standard practice, 19 assessments on novel cancer therapies with likely therapeutic and/or financial impacts have been published. CONCLUSIONS: The successful implementation of an HSS necessitates a repetitive cycle of adjustments in order to meet the objectives set by the individual HSS.

Introduction of organised mammography screening in Tyrol: results following first year of complete rollout.

BACKGROUND: In Tyrol, Austria, the existing system of spontaneous mammography screening was switched in 2007 to an organised program by smoothly changing the established framework. This process followed most EU recommendations for organised mammography screening with the following exceptions: women aged 40-49 are part of the target population, screening is offered annually to the age group 40-59, breast ultrasound is available as an additional diagnostic tool, and double reading has not yet been implemented. After a pilot phase the program was rolled out to all of Tyrol in June 2008. The aim of this study was to analyse the performance of the organised screening system by comparing quality indices and recommended levels given in the well-established EU guidelines. METHODS: Working from the results of the pilot phase, we extended the organised mammography system to all counties in Tyrol. All women living in Tyrol and covered by compulsory social insurance were invited for a mammography, in the age group 40-59 annually and in the age group 60-69 biennially. Screening mammography was offered mainly by radiologists in private practice, with further assessment performed at hospitals. Using the screening database, all well-established performance indicators were analysed and compared with accepted/desired levels as per the EU guidelines. RESULTS: From June 2008 to May 2009, 120,440 women were invited. Per 1000 mammograms, 14 women were recalled for further assessment, nine underwent biopsy and four cancer cases were detected. Of invasive breast cancer cases, 32.3% and 68.4% were ≤ 10 mm and ≤ 15 mm in size, respectively, and 79.2% were node-negative. The positive predictive value for further assessment and for biopsy was 25.9% and 39.9%, respectively. Estimated two-year participation rate was 57.0%. In total, 14 interval cancer cases were detected during one year of follow-up; this is 18.4% of the background incidence rate. CONCLUSIONS: In Tyrol, Austria, an organised mammography screening program was implemented in a smooth transition from an existing spontaneous screening system and was completely rolled out within a short time. The high level of performance already seen in the pilot phase was maintained after rollout, and improvements resulting from the pilot phase were affirmed after one year of complete rollout.

Safety of bevacizumab in patients with advanced cancer: a meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a meta-analysis on adverse events seen with bevacizumab to combine the existing evidence about its safety in patients with advanced cancer. METHODS: A systematic literature search was conducted to identify published, randomized controlled trials of bevacizumab in cancer patients with data on adverse events available. The primary endpoint was "severe adverse event," a composite of grade 3 and 4 adverse events. Secondary endpoints for the exploratory analysis were individual adverse events. We used random-effects meta-analysis to combine data. RESULTS: Thirteen eligible publications were identified and eight trials reported the primary endpoint. Compared with the control group, the bevacizumab group had a slightly higher risk for any severe adverse event (pooled relative risk, 1.10; 95% confidence interval [95% CI], 1.01-1.19). The pooled risk difference was 7% (95% CI, 1%-13%), with a number needed to harm of 14 treated patients. Exploratory analyses showed a statistically significant higher risk for eight of the 15 evaluated secondary endpoints: bevacizumab was associated with a fourfold higher risk for hypertension, epistaxis, and gastrointestinal hemorrhage/perforation; a threefold higher risk for any bleeding events; and a lower, but elevated risk for proteinuria, leukopenia, diarrhea, and asthenia. No statistically significant differences were found for any thrombotic event (arterial or venous), hemoptysis, cardiac event, thrombocytopenia, neutropenia, impaired wound healing, or death related to an adverse event. CONCLUSION: Treatment with bevacizumab was associated with a slightly higher risk for any severe (grade 3 or 4) adverse event in patients with cancer. The result may impact individual benefit-risk assessments and policy guidelines.