Evaluation of the "Burgenland PREvention trial of colorectal cancer Disease with ImmunologiCal Testing" (B-PREDICT)-a population-based colorectal cancer screening program.

BACKGROUND: The colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B-PREDICT was compared with the opportunistic screening colonoscopy (OPP-COL), performed in course of the nationwide screening program. METHODS: Within B-PREDICT all residents of the Austrian federal state Burgenland, aged between 40 and 80 are annually invited to FIT testing. All individuals who underwent initial colonoscopy in Burgenland between 01/2003 and 12/2014, were included in this study. Individuals from the FIT-triggered invited screening program B-PREDICT were compared with those from the non-FIT triggered OPP-COL. RESULTS: 15 133 individuals from B-PREDICT were compared to 10 045 individuals with OPP-COL. CRC detection rates were 1.34% (CI-95%, [1.15; 1.52]) in B-PREDICT compared to 0.54% in OPP-COL (95%-CI, [0.39; 0.68] p < 0.001). The decrease in the age standardized incidence rates of CRC was more pronounced in the population screened with FIT than in the general population screened with colonoscopy. Changes in incidence rates per year were -4.4% (95%-CI, [-5.1; -3.7]) vs. -1.8% (95%-CI, [-1.9; -1.6] p < 0.001). CONCLUSIONS: B-PREDICT shows a two-fold higher detection rate of CRC as well as HRA compared to OPP-COL.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Skin melanoma deaths within 1 or 3 years from diagnosis in Europe.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

Reducing overtreatment associated with overdiagnosis in cervical cancer screening-A model-based benefit-harm analysis for Austria.

A general concern exists that cervical cancer screening using human papillomavirus (HPV) testing may lead to considerable overtreatment. We evaluated the trade-off between benefits and overtreatment among different screening strategies differing by primary tests (cytology, p16/Ki-67, HPV alone or in combinations), interval, age and diagnostic follow-up algorithms. A Markov state-transition model calibrated to the Austrian epidemiological context was used to predict cervical cancer cases, deaths, overtreatments and incremental harm-benefit ratios (IHBR) for each strategy. When considering the same screening interval, HPV-based screening strategies were more effective compared to cytology or p16/Ki-67 testing (e.g., relative reduction in cervical cancer with biennial screening: 67.7% for HPV + Pap cotesting, 57.3% for cytology and 65.5% for p16/Ki-67), but were associated with increased overtreatment (e.g., 19.8% more conizations with biennial HPV + Papcotesting vs. biennial cytology). The IHBRs measured in unnecessary conizations per additional prevented cancer-related death were 31 (quinquennial Pap + p16/Ki-67-triage), 49 (triennial Pap + p16/Ki-67-triage), 58 (triennial HPV + Pap cotesting), 66 (biennial HPV + Pap cotesting), 189 (annual Pap + p16/Ki-67-triage) and 401 (annual p16/Ki-67 testing alone). The IHBRs increased significantly with increasing screening adherence rates and slightly with lower age at screening initiation, with a reduction in HPV incidence or with lower Pap-test sensitivity. Depending on the accepted IHBR threshold, biennial or triennial HPV-based screening in women as of age 30 and biennial cytology in younger women may be considered in opportunistic screening settings with low or moderate adherence such as in Austria. In organized settings with high screening adherence and in postvaccination settings with lower HPV prevalence, the interval may be prolonged.

Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.

BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.

Increasing use of immunotherapy and prolonged survival among younger patients with primary CNS lymphoma: a population-based study.

Background: Primary CNS lymphoma is a highly aggressive and rare type of extranodal non-Hodgkin lymphoma. Although, new therapeutic approaches have led to improved survival, the management of the disease poses a challenge, practice patterns vary across institutions and countries, and remain ill-defined for vulnerable patient subgroups. Material and Methods: Using information from the Austrian Brain Tumor Registry we followed a population-based cohort of 189 patients newly diagnosed from 2005 to 2010 through various lines of treatment until death or last follow-up (12-31-2016). Prognostic factors and treatment-related data were integrated in a comprehensive survival analysis including conditional survival estimates. Results: We find variable patterns of first-line treatment with increasing use of rituximab and high-dose methotrexate (HDMTX)-based poly-chemotherapy after 2007, paralleled by an increase in median overall survival restricted to patients aged below 70 years. In the entire cohort, 5-year overall survival was 24.4% while 5-year conditional survival increased with every year postdiagnosis. Conclusion: In conclusion, we show that the use of poly-chemotherapy and immunotherapy has disseminated to community practice to a fair extent and survival has increased over time at least in younger patients. Annually increasing conditional survival rates provide clinicians with an adequate and encouraging prognostic measure.

Differential role of angiogenesis and tumour cell proliferation in brain metastases according to primary tumour type: analysis of 639 cases.

AIM: We aimed to characterize angiogenesis and proliferation and their correlation with clinical characteristics in a large brain metastasis (BM) series. METHODS: Ki67 proliferation index, microvascular density (MVD) and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry in BM and primary tumour specimens. RESULTS: Six hundred thirty-nine BM specimens of 639 patients with lung cancer (344/639; 53.8%), breast cancer (105/639; 16.4%), melanoma (67/639; 10.5%), renal cell carcinoma (RCC; 52/639; 8.1%) or colorectal cancer (CRC; 71/639; 11.1%) were available. Specimens of the corresponding primary tumour were available in 113/639 (17.7%) cases. Median Ki67 index was highest in CRC BM and lowest in RCC BM (P < 0.001). MVD and HIF-1 alpha index were both highest in RCC BM and lowest in melanoma BM (P < 0.001). Significantly higher Ki67 indices, MVD and HIF-1 alpha indices in the BM than in matched primary tumours were observed for breast cancer, non-small cell lung cancer (NSCLC) and CRC. Correlation of tissue-based parameters with overall survival in individual tumour types showed a favourable and independent prognostic impact of low Ki67 index [hazard ratio (HR) 1.015; P < 0.001] in NSCLC BM and of low Ki67 index (HR 1.027; P = 0.008) and high angiogenic activity (HR 1.877; P = 0.002) in RCC. CONCLUSION: Our data argue for differential pathobiological and clinical relevance of Ki67 index, HIF1-alpha index and MVD between primary tumour types in BM patients. An independent prognostic impact of tissue-based characteristics was observed in patients with BM from NSCLC and RCC, supporting the incorporation of these tissue-based parameters into diagnosis-specific prognostic scores.

Amplification and overexpression of CMET is a common event in brain metastases of non-small cell lung cancer.

BACKGROUND: CMET represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). METHODS: We investigated CMET gene amplification status by fluorescence in-situ hybridization (FISH) and CMET protein expression by immunohistochemistry in a large series of 209 NSCLC brain metastases (BM; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and two large cell neuroendocrine carcinomas) and correlated our results to clinic-pathological parameters and molecular data from previous studies. RESULTS: We found CMET gene amplification in 36/167 (21.6%) and CMET protein expression in 87/196 (44.4%) of evaluable BM. There was a strong correlation between the presence of CMET gene amplification and CMET protein expression (P < 0.001, chi-square test). Furthermore, presence of CMET amplification correlated positively with presence of ALK amplifications (P = 0.039, chi-square test) and high HIF1 alpha index (P = 0.013, Mann-Whitney U-test). Neither CMET expression nor CMET gene amplification status correlated with patient outcome parameters or known prognostic factors. CONCLUSIONS: CMET overexpression and CMET amplification are commonly found in NSCLC BM and may represent a promising therapeutic target.

Time Trends in Male Breast Cancer Incidence, Mortality, and Survival in Austria (1983-2017).

Background: Male breast cancer (MBC) comprises less than 1% of all breast cancer cases globally and remains understudied with persisting sex-specific survival disadvantages. We aim to contribute to better understanding of MBC with a comprehensive analysis of time-trends over several decades in Austria. Methods: We used Austrian National Cancer Registry data on 1648 cases of MBC cases diagnosed between 1983 and 2017 in Austria. Overall incidence, mortality, and survival rates, as well as age-, stage-, and period-specific incidence and survival rates were calculated. Joinpoint regression was performed to assess trends. Results: MBC incidence rates increased throughout the whole observation period (1983-2017) with an annual percent change (APC) of 1.44% (95% confidence interval, CI: 0.77 to 2.11). During the same period, morality rates were stable (APC: -0.25, 95% CI: -0.53 to 0.60). Ten-year survival rates showed three phases of decreasing increases with an average APC of 2.45%, 1983-2009 (95% CI: 2.1 to 2.74). Five-year survival rates improved until 2000 (APC: 2.31, 95% CI: 1.34 to 3.30) and remained stable thereafter (APC: 0.10, 95% CI: -0.61 to 0.80). Stage-specific analyses showed a single trend of stable incidence rates of distant disease MBC (APC: -0.03, 95% CI: -1.67 to 1.65). Further, we observed increases in localised, regional, and unknown stage cancer incidence and increases in incidence rates across all age groups over the whole observation period. However, the estimates on these subgroup-specific trends (according to age- and stage) show wider 95% CIs and lower bounds closer to zero or negative in comparison to our findings on overall incidence, mortality, and survival. Conclusion: Despite improvements in survival rates, MBC mortality rates remained largely stable between 1983 and 2017 in Austria, possibly resulting from a balance between increasing overall incidence and stable incidence rates of distant disease MBC.

Estimation of completeness of case ascertainment of Austrian cancer incidence data using the flow method.

BACKGROUND: The international comparability of data from population-based cancer registries depends strongly on the completeness of case ascertainment. Furthermore, Austrian observed incidence rates suggest that the completeness of case ascertainment differs between Austrian federal states. Completeness of case ascertainment is to be investigated on national and regional level. METHODS: We used the flow method to evaluate the completeness of the Austrian National Cancer Registry. This method is based on the logical flow of data in the registration system, and on the time distribution of various probabilities inherent in this flow. RESULTS: Overall completeness of the Austrian cancer incidence data 2005 was 94.2% after a registration period of 5 years. The flow method found striking differences in completeness between the federal states, which are contrary to the time series analyses. CONCLUSION: Overall completeness of the Austrian National Cancer Registry is in concordance with estimates from international registries. The biggest part of the decrease of incidence rates in the past 2 published years seems to be a result of incompleteness. The importance of the registration date of a cancer case and the survival time on completeness estimation using the flow method has become apparent. Further investigation into the comparability of registration date between the federal states and into the quality of survival time estimates is recommended.

Increase and Plateauing of Testicular Cancer Incidence in Austria-A Time Trend Analysis of the Past Four Decades.

Background: Testicular germ cell tumors (TGCTs) are the most common malignant tumors in young men. Despite considerable geographic, ethnic, and temporal variations in the incidence of TGCTs, without convincing explanation, incidence rates of TGCTs have been increasing in many countries since, at least, the mid-20th century. Objective: To investigate the incidence rates of TGCTs in Austria by analyzing data from the Austrian Cancer Registry. Design setting and participants: Available data between 1983 and 2018 were provided by the Austrian National Cancer Registry and analyzed retrospectively. Outcome measurements and statistical analysis: Germ cell tumors derived from germ cell neoplasia in situ were classified into seminomas and nonseminomas. Age-specific incidence rates and age-standardized rates were calculated. Annual percent changes (APCs) and average annual percent changes in incidence rates were determined to describe trends from 1983 to 2018. All statistical analyses were performed using SAS version 9.4 and joinpoint. Results and limitations: The study population consists of 11 705 patients diagnosed with TGCTs. The median age at diagnosis was 37.7 yr. The standardized incidence rate of TGCTs increased significantly (p < 0.0001) from 4.1 (3.4, 4.8) per 100 000 in 1983 to 8.7 (7.9, 9.6) per 100 000 in 2018 by an average APC of 1.74 (1.20, 2.29). The joinpoint regression revealed a change point in time trend in 1995 with an APC of 4.24 (2.77, 5.72) before 1995 and an APC of 0.47 (0.06, 0.89) thereafter. Incidence rates were about twice as high for seminomas as for nonseminomas. A trend analysis by age group showed that the highest TGCT incidence rate was observed among men aged 30-40 yr, with a steep increase before 1995. Conclusions: The incidence rate of TGCTs increased in Austria over the past decades and appears to have reached a plateau at a high level. A time trend analysis by age group for the overall incidence was highest in men aged 30-40 yr, with a steep increase before 1995. These data should lead to awareness campaigns and research to further investigate the causes of this development. Patient summary: We reviewed the data between 1983 and 2018 provided by the Austrian National Cancer Registry to analyze the incidence and incidence trend in testicular cancer. Testicular cancer shows an increasing incidence in Austria. The overall incidence was highest in men aged 30-40 yr, with a steep increase before 1995. The incidence appears to have reached a plateau at a high level in recent years.

Colorectal Cancer and Precursor Lesion Prevalence in Adults Younger Than 50 Years Without Symptoms.

Importance: Incidence of colorectal cancer (CRC) is increasing among younger adults. However, data on precursor lesions in patients who are asymptomatic, especially those aged younger than 50 years, are lacking. Objective: To analyze the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas, and serrated lesions, as well as the incidence of CRC in patients older than age 20 years. Design, Setting, and Participants: This cohort study was conducted among 296 170 patients who received a screening colonoscopy within a national screening colonoscopy registry from 2012 to 2018 in Austria, including 11 103 patients aged younger than 50 years. CRC incidence was analyzed using data from Statistic Austria from 1988 to 2018. Data were analyzed in September 2021. Main Outcome and Measures: The prevalence of adenomas and other lesions and the incidence of CRC in individuals aged 20 years or older were assessed. Results: Among 296 170 patients included in the study (median [IQR] age, 60 [54-68] years; 150 813 females [50.9%]), 11 103 patients (3.7%) were aged younger than 50 years and 285 067 patients (96.3%) were aged 50 years or older. Among patients younger than age 50 years, 1166 individuals (10.5%; NNS = 9) had adenomas and 389 individuals (3.9%; NNS = 26) had at least 1 advanced adenoma, while among those aged 50 years or older, 62 384 individuals (21.9%; NNS = 5) had adenomas and 19 680 individuals (6.9%; NNS = 15) had at least 1 advanced adenoma. Among 1128 males aged 40 to 44 years, 160 individuals (14.2%; NNS = 7) had at least 1 adenoma, and among 1398 females aged 40 to 44 years, 114 individuals (8.1%; NNS = 12) had at least 1 adenoma. The prevalence of adenomas for individuals aged 45 to 49 years vs 50 to 54 years was 490 of 2879 males (17.1%; NNS = 6) vs 8269 of 40 935 males (20.2%; NNS = 5) and 284 of 2792 females (10.2%; NNS = 10) vs 4997 of 40 303 females (12.4%; NNS = 8), respectively. Prevalence of adenomas changed from 61 of 498 individuals (12.4%) in 2008 to 150 of 1064 individuals (14.1%) in 2018 among those younger than 50 years and from 2646 of 12 166 individuals (21.8%) to 10 673 of 37 922 individuals (28.2%) among those aged 50 years and older. The prevalence of advanced adenomas changed from 20 individuals (4.0%) in 2008 to 55 individuals (5.2%) in 2018 in individuals younger than 50 years and from 888 individuals (7.3%) in 2008 to 2578 individuals (6.8%) in 2018 among those aged 50 years and older. Among individuals younger than age 50 years, CRC incidence per 100 000 individuals changed from 9.1 incidents in 1988 to 10.2 incidents in 2018 among males (average annual percentage change [AAPC], 0.5%; 95% CI, 0.1% to 1.0%) and from 9.7 incidents in 1988 to 7.7 incidents in 2018 among females, with a nonsignificant AAPC (-0.2%; 95% CI, -0.7% to 0.3%). Among individuals aged 50 years or older, CRC incidence per 100 000 individuals changed from 168 incidents in 1988 to 97 incidents in 2018 among females (AAPC, -1.8%; 95% CI, -1.9% to -1.6%), and 217 incidents in 1988 to 143 incidents in 2018 among males (AAPC, -1.2%; 95% CI, -1.3% to -1.1%). Conclusion: In this study, CRC incidence decreased after 1988 in Austria among individuals older than 50 years, while among patients younger than 50 years, incidence increased among males but decreased among females. Prevalence of adenomas increased in all age groups, while advanced adenoma prevalence increased among patients younger than 50 years but decreased in patients aged 50 years and older.

Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study.

Colorectal cancer (CRC) is the second most common cause of death due to cancer causing death in Europe, accounting for more than 200,000 deaths per year. Prognosis strongly depends on stage at diagnosis, and the disease can be cured in most cases if diagnosed at an early stage. We aimed to assess trends and recent developments in 5-year relative survival in European countries, with a special focus on age, stage at diagnosis and anatomical cancer subsite. Data from 25 population-based cancer registries from 16 European countries collected in the context of the EUROCARE-4 project were analyzed. Using period analysis, age-adjusted and age-specific 5-year relative survival was calculated by country, European region, stage and cancer subsite for time periods from 1988-1990 to 2000-2002. Survival substantially increased over time in all European regions. In general, increases were more pronounced in younger than in older patients, for earlier than for more advanced cancer stages and for rectum than for colon cancer. Substantial variation of CRC survival between European countries and between age groups persisted and even tentatively increased over time. There is a huge potential for reducing the burden of CRC in Europe by more widespread and equal delivery of existing options of effective early detection and curative treatment to the European population.

Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases.

Brain metastases (BM) are frequent and carry a dismal prognosis. BRAF V600E mutations are found in a broad range of tumor types and specific inhibitors targeting BRAF V600E protein exist. We analyzed tumoral BRAF V600E-mutant protein expression using the novel mutation-specific antibody VE1 in a series of 1,120 tumor specimens (885 BM, 157 primary tumors, 78 extra-cranial metastases) of 874 BM patients. In 85 cases, we performed validation of immunohistochemical results by BRAF exon 15 gene sequencing. BRAF V600E protein was expressed in BM of 42/76 (55.3%) melanomas, 1/15 (6.7%) ovarian cancers, 4/72 (5.5%) colorectal cancers, 1/355 (0.3%) lung cancers, 2/6 thyroid cancers and 1/2 choriocarcinomas. BRAF V600E expression showed high intra-tumoral homogeneity and was similar in different tumor manifestations of individual patients. VE1 immunohistochemistry and BRAF exon 15 sequencing were congruent in 68/70 (97.1%) cases, but VE1 immunostaining identified small BRAF V600E expressing tumor cell aggregates in 10 cases with inconclusive genetic results. Melanoma patients with BRAF V600E mutant protein expressing tumors were significantly younger at diagnosis of the primary tumor and at operation of BM than patients with non-mutated tumors. In conclusion, expression of BRAF V600E mutant protein occurs in approximately 6% of BM and is consistent in different tumor manifestations of the same patient. Thus, BRAF V600E inhibiting therapies seem feasible in selected BM patients. Immunohistochemical visualization of V600E-mutant BRAF protein is a promising tool for patient stratification. An integrated approach combining both, VE1 immunohistochemistry and genetic analysis may increase the diagnostic accuracy of BRAF mutation analysis.

Trends in female breast cancer incidence, mortality, and survival in Austria, with focus on age, stage, and birth cohorts (1983-2017).

Breast cancer (BC) is the most commonly diagnosed malignant disease and the leading cause of cancer death in women in Austria. We investigated overall and subgroup-specific female breast cancer rates to provide a comprehensive analysis of trends over several decades. Incidence, mortality, and survival, as well as age-, stage-, and birth cohort-specific incidence were analysed using nationwide cancer registry data on 163,694 cases of female breast cancer in Austria (1983-2017). Annual percentage changes were estimated using joinpoint regression. BC incidence underwent linear increases until 1997 and reversed with statistically non-significant declines until 2017. After initial increases in BC-specific mortality, rates were stable from 1989 through 1995 and started declining thereafter, although statistically non-significantly after 2011. Overall BC-specific survivals, as well as survivals according to the calendar period of diagnosis, increased throughout the observation period. Incidence in younger women (aged 44 and lower) showed linear increases, whereas for women aged 45 and higher mostly stable or decreasing rates were observed. Localised BC incidence increased markedly and started declining only in 2012. Distant disease-BC incidence decreased through the whole observation period and incidence of regionalised BC started declining in 2000. Birth cohort-specific incidence peaked in women born between 1935 and 1949 (ages 45-74). In conclusion, the incidence of BC in younger women is increasing, while overall female BC incidence and mortality are stable with non-significant declines. Further, increases in the incidence of early-stage BC (localised) seem disproportionately high in comparison to more modest decreases in late-stage BC incidence (regionalised and distant disease).

Changing Epidemiological Trends of Hepatobiliary Carcinomas in Austria 2010-2018.

Using national registries, we investigated the epidemiological trends of hepatobiliary carcinomas in Austria between 2010 and 2018 and compared them to those reported for the periods of 1990-1999 and 2000-2009. In total, 12,577 patients diagnosed with hepatocellular carcinoma (n = 7146), intrahepatic cholangiocarcinoma (n = 1858), extrahepatic cholangiocarcinoma (n = 1649), gallbladder carcinoma (n = 1365), and ampullary carcinoma (n = 559), between 2010 and 2018, were included. The median overall survival of all patients was 9.0 months. The best median overall survival was observed in patients with ampullary carcinoma (28.5 months) and the worst median overall survival was observed in patients with intrahepatic carcinoma (5.6 months). The overall survival significantly improved in all entities over the period 2010-2018 as compared with over the periods of 2000-2009 and 1990-1999. Age-adjusted incidence and mortality rates remained stable for most entities in both, men and women; only in gallbladder carcinoma, the incidence and mortality rates significantly decreased in women, whereas, in men, the incidence rates remained stable and mortality rates showed a decreasing trend. We showed that age-adjusted incidence and mortality rates were stable in most entities, except in gallbladder carcinoma. The overall survival improved in almost all entities as compared with those during 1990-2009.

Moderate Altitude Residence Reduces Male Colorectal and Female Breast Cancer Mortality More Than Incidence: Therapeutic Implications?

BACKGROUND: Living at moderate altitude may be associated with health benefits, including reduced mortality from male colorectal and female breast cancer. We aimed to determine altitude-dependent incidence and mortality rates of those cancers and put them in the context of altitude-associated lifestyle differences. METHODS: Incidence cases and deaths of male colorectal cancer (n = 17,712 and 7462) and female breast cancer (n = 33,803 and 9147) from altitude categories between 250 to about 2000 m were extracted from official Austrian registries across 10 years (2008-2017). Altitude-associated differences in health determinants were derived from the Austrian Health Interview Survey (2014). RESULTS: The age-standardized incidence and mortality rates of male colorectal cancer decreased by 24.0% and 44.2%, and that of female breast cancer by 6.5% and 26.2%, respectively, from the lowest to the highest altitude level. Higher physical activity levels and lower body mass index for both sexes living at higher altitudes were found. CONCLUSIONS: Living at a moderate altitude was associated with a reduced incidence and (more pronounced) mortality from colorectal and breast cancer. Our results suggest a complex interaction between specific climate conditions and lifestyle behaviours. These observations may, in certain cases, support decision making when changing residence.

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec (p = 0.008) and Jan-Mar (p < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

Trends in incidence of anal cancer in Austria, 1983-2016.

BACKGROUND: Recent reports have noted increasing rates of anal cancer among high-income countries worldwide; however, little is known about these trends in Austria. METHODS: Data on anal cancer from 1983 to 2016 were obtained from Statistics Austria. All tumors (n = 3567) were classified into anal squamous cell carcinomas (ASCC), anal adenocarcinomas (AADC), and others (unspecified carcinoma and other specific carcinoma). Anal cancer incidence rates were calculated in 5­year cycles and incidence average annual percentage change (AAPC) to evaluate trends by sex, histology and age group. RESULTS: The incidence rate of anal cancer was higher among females than males (relative risk, RR = 1.66, 95% confidence interval, CI: 1.55-1.79, p < 0.0001). From 1983 through 2016, incident anal cancer increased significantly (0.92 per 100,000 person-years to 1.85 per 100,000 person-years, AAPC = 1.93, 95% CI: 1.52 to 2.34, p < 0.0001), particularly among those 40-69 years old. From 1983 through 2016, the increasing anal cancer incidence was primarily driven by ASCC (0.47-1.20 per 100,000 person-years, AAPC = 2.23, 95% CI: 1.58 to 2.88, p < 0.0001) and others (other than ASCC and AADC, AAPC = 1.78, 95% CI: 1.01-2.55), yet stable in AADC (AAPC = 0.88, 95% CI: -0.48-2.25). CONCLUSIONS: Despite being a rare cancer in Austria, the increase in anal cancer incidence rate from 1983 to 2016 was substantial, particularly in ASCC. The observed rising trends reflect the need to investigate associated risk factors that have increased over time to inform preventive measures.

The Austrian Brain Tumour Registry: a cooperative way to establish a population-based brain tumour registry.

In Austria, registration of malignant brain tumours is legally mandatory, whereas benign and borderline tumours are not reported. The Austrian Brain Tumour Registry (ABTR) was initiated under the auspices of the Austrian Society of Neuropathology for the registration of malignant and non-malignant brain tumours. All Austrian neuropathology units involved in brain tumour diagnostics contribute data on primary brain tumours. Non-microscopically verified cases are added by the Austrian National Cancer Registry to ensure a population-based dataset. In 2005, we registered a total of 1,688 newly diagnosed primary brain tumours in a population of 8.2 million inhabitants with an overall age-adjusted incidence rate of 18.1/100,000 person-years. Non-malignant cases constituted 866 cases (51.3%). The incidence rate was higher in females (18.6/100,000) as compared to males (17.8/100,000), while 95/1,688 (5.6%) cases were diagnosed in children (<18 years). The most common histology was meningioma (n = 504, 29.9%) followed by glioblastoma (n = 340, 20.1%) and pituitary adenoma (n = 151, 8.9%). Comparison with the Central Brain Tumor Registry of the United States (CBTRUS) database showed high congruency of findings. The ABTR model led by neuropathologists in collaboration with epidemiologists and the Austrian National Cancer Registry presents a cooperative way to establish a population-based brain tumour registry with high quality data. This setting links cancer registration to the mission of medical practice and research as defined by the World Medical Association in the Declaration of Helsinki. The continued operation of ABTR will aid in monitoring changes in incidence and in identifying regional disease clusters or geographic variations in brain tumour morbidity/mortality.