Differences in Treatment and Outcome of Pancreatic Adenocarcinoma Stage I and II in the EURECCA Pancreas Consortium.

BACKGROUND: The EUropean REgistration of Cancer CAre (EURECCA) consortium aims to investigate differences in treatment and to improve cancer care through Europe. The purpose of this study was to compare neo- and adjuvant chemotherapy (ACT) and outcome after tumor resection for pancreatic adenocarcinoma stage I and II in the EURECCA Pancreas consortium. METHODS: The eight, collaborating national, regional, and single-center partners shared their anonymized dataset. Patients diagnosed in 2012-2013 who underwent tumor resection for pancreatic adenocarcinoma stage I and II were investigated with respect to treatment and survival and compared using uni- and multivariable logistic and Cox regression analyses. All comparisons were performed separately per registry type: national, regional, and single-center registries. RESULTS: In total, 2052 patients were included. Stage II was present in the majority of patients. The use of neo-ACT was limited in most registries (range 2.8-15.5%) and was only different between Belgium and The Netherlands after adjustment for potential confounders. The use of ACT was different between the registries (range 40.5-70.0%), even after adjustment for potential confounders. Ninety-day mortality was also different between the registries (range 0.9-13.6%). In multivariable analyses for overall survival, differences were observed between the national and regional registries. Furthermore, patients in ascending age groups and patients with stage II showed a significant worse overall survival. CONCLUSIONS: This study provides a clear insight in clinical practice in the EURECCA Pancreas consortium. The differences observed in (neo-)ACT and outcome give us the chance to further investigate the best practices and improve outcome of pancreatic adenocarcinoma.

Common variables in European pancreatic cancer registries: The introduction of the EURECCA pancreatic cancer project.

BACKGROUND: Quality assurance of cancer care is of utmost importance to detect and avoid under and over treatment. Most cancer data are collected by different procedures in different countries, and are poorly comparable at an international level. EURECCA, acronym for European Registration of Cancer Care, is a platform aiming to harmonize cancer data collection and improve cancer care by feedback. After the prior launch of the projects on colorectal, breast and upper GI cancer, EURECCA's newest project is collecting data on pancreatic cancer in several European countries. METHODS: National cancer registries, as well as specific pancreatic cancer audits/registries, were invited to participate in EURECCA Pancreas. Participating countries were requested to share an overview of their collected data items. Of the received datasets, a shared items list was made which creates insight in similarities between different national registries and will enable data comparison on a larger scale. Additionally, first data was requested from the participating countries. RESULTS: Over 24 countries have been approached and 11 confirmed participation: Austria, Belgium, Bulgaria, Denmark, Germany, The Netherlands, Slovenia, Spain, Sweden, Ukraine and United Kingdom. The number of collected data items varied between 16 and 285. This led to a shared items list of 25 variables divided into five categories: patient characteristics, preoperative diagnostics, treatment, staging and survival. Eight countries shared their first data. CONCLUSIONS: A list of 25 shared items on pancreatic cancer coming from eleven participating registries was created, providing a basis for future prospective data collection in pancreatic cancer treatment internationally.

Trends in incidence and predictions of cutaneous melanoma across Europe up to 2015.

BACKGROUND: Melanoma is a significant health problem in Caucasian populations. The most recently available data from cancer registries often have a delay of several months up to a few years and they are generally not easily accessible. OBJECTIVES: To assess recent age- and sex-specific trends in melanoma incidence and make predictions for 2010 and 2015. METHODS: A retrospective registry-based analysis was performed with data from 29 European cancer registries. Most of them had data available from 1990 up to 2006/7. World-standardized incidence rates (WSR) and the estimated annual percentage change (EAPC) were computed. Predictions were based on linear projection models. RESULTS: Overall the incidence of melanoma is rapidly rising and will continue to do so. The incidence among women in Europe was generally higher than in men. The highest incidence rates were seen for Northern and north-western countries like the UK, Ireland and the Netherlands. The lowest incidence rates were observed in Portugal and Spain. The incidence overall remained stable in Norway, where, amongst young (25-49 years) Norwegian males rates significantly decreased (EAPC -2.8, 95% CI -3.6; -2.0). Despite a low melanoma incidence among persons above the age of 70, this age group experienced the greatest increase in risk during the study period. CONCLUSIONS: Incidence rates of melanoma are expected to continue rising. These trends are worrying in terms of disease burden, particularly in eastern European countries.

Breast cancer incidence trends in European women aged 20-39 years at diagnosis.

An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and 1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straightforward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden of the disease that is important in terms of public health and deserves further investigation of possible risk factors.

Review of negative and low-grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia.

OBJECTIVE: The purpose of the study was to perform a national review of negative, low-grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. METHODS: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high-grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low-grade, atypical or inadequate smear 1-40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. RESULTS: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty-one of 37 women also had high-grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high-grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno- and adenosquamous carcinomas (5/24, P < 0.05). CONCLUSION: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under-diagnosed smears were not related to cancer stage or last cytology report before diagnosis.

Performance of opportunistic breast cancer screening in Slovenia.

The purpose of the study was to assess performance indicators of opportunistic breast screening carried out in one of the Primary Breast Diseases Centers (PBDC) and to find out if these indicators meet the standards set in "European guidelines for quality assurance in mammographic screening". The records of 1,896 asymptomatic women, aged between 50 and 69 years who attended PBDC for the first time in the period from October 15 1998 to October 15 2002, were reviewed. In all of them, clinical examination and mammography was done. If necessary, non-invasive additional imaging was also performed in the PBDC. If malignancy could not be excluded, the women were referred to the Institute of Oncology (IO) for additional invasive diagnostic procedures. The data on these findings were collected from the records of the IO. We compared our results with the recommended values of performance indicators valid for organized screening programs as determined by "European guidelines". Of 1,896 women, 415 (22%) were recalled for additional imaging. In 335/415 women the suspicion for malignancy was excluded with noninvasive diagnostic methods. Invasive diagnostic procedures were applied in 80/415 women. Carcinomas were detected in 23 women, the majority of them (96%) were non palpable. All carcinomas were ductal; 9 (39%), 7 (30.5%), 7 (30.5%) were grade 1, 2 and 3, respectively. One carcinoma was preinvasive; 20 had the tumor size T1, 1 had T2, while in one the size was not specified. The axillary lymph nodes were negative in 14/23 (61%) women with invasive carcinoma and positive in 5/23 (22%). Surgery of the axilla was considered unnecessary in 4/23 (17%). Diagnostic sensitivity in presented cohort was 96%, specificity 79%. After a negative mammogram 1 interval cancer was detected. Compared to the "European guidelines" we achieved satisfactory results in the number and size of detected and interval cancers, but the analysis showed a higher recall rate with too many false-positive results. Efforts should target lowering the recall rate without reducing the cancer detection rate. Compared to Slovenian average, a large percentage of localized breast cancers in our study claim for organized breast cancer screening program in Slovenia at earliest convenience.

The association between induced and spontaneous abortion and risk of breast cancer in Slovenian women aged 25-54.

The risk of breast cancer may be increased by induced or spontaneous abortion. The evidence for this association was evaluated in a population based case-control study in Slovenia, where 624 women aged 25-54 years with breast cancer diagnosed during 1988-1990 were matched for age and site of residence with controls randomly selected from the Slovenian Population Registry. Odds ratios (OR) and 95% confidence intervals (CI) were obtained by conditional logistic regression analyses. Spontaneous abortion was not associated with a significantly increased risk of breast cancer (nulliparous women: OR=1.41, 95% CI 0.22-9.01; uniparous women: OR=0.98, 95% CI 0.50-1.91; women with parity 2 or more: OR=1.40, 95% CI 0.91-2.15). Induced abortion was not associated with a statistically significant elevated risk. The risk of breast cancer was higher in nulliparous women (OR=2.49, 95% Cl 0.68-9.09), and was less among women who had more deliveries. In uniparous women, the risk of breast cancer appeared higher when the induced abortion took place before a first full-term pregnancy (OR=1.94, 95% CI 0.70-5.39) rather than after a first full-term pregnancy (OR=1.22, 95% CI 0.71-2.10) but neither of these odds ratios reached significance. We found no significant association between spontaneous abortion or induced abortion and breast cancer risk. This study found an elevated, but not statistically significant, risk associated with induced abortion among nulliparous women and among parous women when the induced abortion was before the first full-term pregnancy.

Breast cancer incidence rates in Slovenia 1971-1993.

BACKGROUND: Analyses of time trends in breast cancer incidence and mortality have generally revealed cohort-based changes in the rates. These have been linked to cohort-based changes in lifestyle factors. The effect of the changes in the reproductive risk factors on the changes in the rates, and the relative importance of the reproductive characteristics in Slovenia, a country which has not had much breast cancer screening, are investigated. METHODS: Data on breast cancer incidence for 1971-1993 were obtained from the Cancer Registry of Slovenia (Registry). The Registry covers the whole population of the Republic of Slovenia (1.99 million on 30 June 1993). The statistical analysis uses parametric age-period-cohort models. RESULTS: Breast cancer incidence has increased by 70% in Slovenia from 1971 to 1993, These changes are dominated by cohort effects and the cohorts born in 1907-1922 have the greatest increase in incidence. Period effects on changes in incidence were modest. The percentage of nulliparous women in the cohort and the average family size in the cohort explained 38% of the variation in the cohort effects. CONCLUSIONS: The percentage of nulliparous women in the cohort is the most important reproductive variable associated with the trends in the rates, with breast cancer risk predicted to be higher in cohorts with a larger percentage of nulliparous women. As the cohorts born 1932-1946 have a more favourable reproductive pattern as regards breast cancer risk, compared to the 1907-1922 cohorts, age-specific incidence rates in Slovenia would be predicted to decline in the future in the absence of changes in the other risk factors.

Future trends in breast, cervical, lung, mouth and pharyngeal cancer incidence in Slovenia.

OBJECTIVES: Breast, cervical, lung, mouth and pharyngeal cancers are important public health problems in Slovenia, and in many other Central and South European countries. The aim of this study was to predict the incidence of these cancers in Slovenia up to the year 2009, based on the data of the Cancer Registry of Slovenia for the period 1965-1994 and on the official national population projections for the Republic of Slovenia. METHODS: Age-period-cohort models were applied. In the case of data heterogeneity in lung as well as in mouth and oropharyngeal cancer in males, an additional parameter indicating differences in lifestyle was introduced in the model. RESULTS: After accounting for major site-specific risk factors, we predict in females a steady increase in breast and lung cancer, but no major changes in cervical cancer case-load. In males a steady decrease in the lung cancer case-load is expected throughout the predicted period, while for mouth and pharyngeal cancer a moderate decrease is expected only after the year 2000. CONCLUSION: Despite some uncertainties inherent in cancer incidence predictions, the obtained results are important in setting priorities for national cancer control strategies in Slovenia, especially in further efforts towards primary prevention of lung, mouth and pharyngeal cancer, and in more efficient early detection of breast, cervical, mouth and pharyngeal cancer.

Screening mammography for early detection of breast cancer.

From numerous studies on breast cancer it can be concluded that no single measure can lessen the burden of this frequent cancer in women in all developed countries. Complex strategies including primary prevention by identification of risk factors and their modification, secondary prevention by earlier detection and tertiary prevention by improving treatment outcome are needed to control the disease. Besides age, the established breast cancer risk factors include certain benign breast diseases, family history, ionising radiation, some reproductive factors and obesity. Primary prevention includes general recommendation for healthy lifestyle, e.g., avoidance of obesity, proper diet, physical activity and moderate alcohol consumption. Randomised controlled trials conducted in the USA, Canada, Scotland and Sweden have shown that regular mammography, alone or in combination with clinical examination, is effective in reducing mortality for about 30% in women over the age of 50, and much less in younger population. However, mammography screening has several drawbacks, the major being its tendency towards false positive and false negative results with all their potential psychosocial consequences. High quality assurance and control, as well as effective and readily available treatment, all of which demand high investments, are indispensable for good results. Even in the absence of organised screening, the availability of effective treatment may contribute to reduction in breast cancer mortality.

Effect of parity and age at delivery on breast cancer risk in Slovenian women aged 25-54 years.

In 1988, a case-control study on breast cancer and oral contraceptives with 624 cases and 624 matched controls in the age range 25-54 years was undertaken in Slovenia. This analysis assesses the relationship between parity and breast cancer risk: the relative importance of age at first birth, age at subsequent births and total parity. We also evaluate whether a dual effect of an increased risk immediately after childbirth followed by a long-term benefit exists. Three logistic regression models were used. Age at first delivery is an important breast cancer risk factor: among parous women it was associated with a 5.3% increase/year in the odds of breast cancer. Multiparity was not shown to be an independent risk factor. Age at subsequent deliveries was associated with a 1% increase in risk for every 1 year increase of age at any birth, but this contribution to the risk was not significant. In the analysis stratified by parity the most important influence is with the age at first birth. We find no evidence of an effect on the odds of breast cancer associated with the age at the second, or later, births. We do find that there is an increased risk associated with the birth of the first child followed by a longer term protective effect. A post-menopausal woman has a reduced breast cancer risk compared with a pre-menopausal woman of the same age, adjusting for the same number of deliveries and ages at these deliveries.

Breast-cancer risk and oral contraceptive use in Slovenian women aged 25 to 54.

Results of a previous case-control study in Slovenia showed a significantly elevated risk of breast cancer for ever-OC users aged 25 to 54 years. A further study was conducted in 1988-1990 in the whole of Slovenia, employing more rigorous epidemiological methodology. Cases were 624 women with breast cancer, aged 25 to 54 years, diagnosed at the Institute of Oncology in Ljubljana and other Slovenian hospitals. Controls were 624 women identified through the Population Registry, randomly selected and matched with cases by date of birth and commune of residence. Data were collected by personal interview, using coloured photographs of packages of all OC on the Slovenian market since 1964. A calendar of reproductive life events was constructed with participants to improve estimation of exposure. The adjusted odds ratio (OR) for ever-users was 1.09. There was no increase in risk with total duration of use, interval since first use, age at starting OC, according to use before or after first delivery and time between menarche and age at first use. Increased risk (OR = 2.92) was found for OC users at the time of diagnosis and for those stopping them less than 6 months before (current users). The risk was not increased for those who stopped OC more than 6 months before diagnosis. The results of this study are consistent with most studies showing no overall effect of OC in women aged till 55 years ever using them. Increased risk of breast cancer in current OC users suggests a possible promoting effect of the pill in susceptible women, and indicates the need for careful breast surveillance of these women while they are using OC and in the period immediately following cessation.

Epidemiological evaluation of cervical cancer screening in Slovenia up to 1986.

In 1986 invasive cervical cancer (CC) in Slovenia, with its incidence rate of 15/100.000, was still the sixth most common cancer in females. In the period 1977-1986 the incidence was stabilized. However, in the age group 60-64 the trend increased steeply (5.3%). The incidence of the intraepithelial form was stabilized after the year 1981, the rates were increasing in the age group 30-39 (3.3%) only. On average, the intraepithelial/invasive CC ratio in Slovenia was 1.2. The ratios differed by communes, however. In 35 of 60 communes they were under 1, the median value being 0.8 only. The mortality rates due to CC differed by regions too. Relatively high invasive CC incidence rates (25-36/100.000) accompanied by a low intraepithelial/invasive CC ratio, and relatively high mortality rates (9.7 and 10.5/100.000) were observed in the health region Maribor, and in the three coastal communes (Piran, Izola, Koper). An independent analysis in depth of Ljubljana region revealed a stabilization in the incidence (15/100.000) as well as in mortality (5.6/100.000) in the last decade too. A better organized screening program is needed in Slovenia. At least in the high-risk regions a systematic screening every three year after two negative smears for all sexually active women aged 27-55 years should be introduced and carried out.

Leukaemia and residence near electricity transmission equipment: a case-control study.

A population-based case-control study of leukaemia and residential proximity to electricity supply equipment has been carried out in south-east England. A total of 771 leukaemias was studied, matched for age, sex, year of diagnosis and district of residence to 1,432 controls registered with a solid tumour excluding lymphoma; 231 general population controls aged 18 and over from one part of the study area were also used. The potential for residential exposure to power frequency magnetic fields from power-lines and transformer substations was assessed indirectly from the distance, type and loading of the equipment near each subject's residence. Only 0.6% of subjects lived within 100 m of an overhead power-line, and the risk of leukaemia relative to cancer controls for residence within 100 m was 1.45 (95% confidence interval (CI) 0.54-3.88); within 50 m the relative risk was 2.0 but with a wider confidence interval (95% CI 0.4-9.0). Over 40% of subjects lived within 100 m of a substation, for which the relative risk of leukaemia was 0.99. Residence within 25 m carried a risk of 1.3 (95% CI 0.8-2.0). Weighted exposure indices incorporating measures of the current load carried by the substations did not materially alter these risks estimates. For persons aged less than 18 the relative risk of leukaemia from residence within 50 m of a substation was higher than in adults (PR = 1.5, 95% CI 0.7-3.4).

A case-control study of breast cancer in relation to oral contraceptive use in Slovenia.

With the aim to investigate a possible association between oral contraceptive (OC) use and breast cancer occurrence, 534 women aged 24--54 years with newly diagnosed breast cancer and 1989 individually matched hospital controls were interviewed during 1980--1983. The overall risk for ever-users vs. never-users estimated by logistic regression and adjusted for several possible confounding factors was 1.62 (p less than 0.05). The analysis of potential biases indicated that this risk may be overestimated, especially because the controls might not be fully representative of the basic population. The risk was increasing with total duration of OC use, reaching the highest value by more than 7 years of use. As to the latency, the risk was the highest for women starting pill use 4--8 years before diagnosis, thus suggesting that OCs might act as promoters rather than initiators of tumor growth. There was no substantial difference in risk between women starting pill use before 25 years of age and those starting it later. The number of users before first term pregnancy was too small to warrant relative risk estimation. Interaction (significant) was found between OC use and family history of breast cancer; there was no such evidence in other subgroups of women being at baseline breast cancer risk. There were no significant differences in the distribution of cases and controls classified by individual OC formulations used. The increased relative risk for users was concentrated in early stages of breast cancer, most likely owing to detection bias. Considering the indicated biases, the results of the study may not be quite conclusive as to the adverse effect of OCs on the breast, but they call for further investigation of this problem.

Epidemiological evaluation of early detection of cervical cancer in Slovenia till 1981.

Cervical cancer screening is performed in all Slovenia in connection with normal clinical practice since 1960. The results based on the data of Cancer Registry of Slovenia: trends in age, specific incidence rates and the distribution of intraepithelial and invasive cervical cancer incidence rates by communes revealed that cervical cancer screening is efficient in Slovenia; in two commune aggregates only and up to the age 40. A detailed analysis of cases of FIGO stage I into Ia and Ib stage demonstrated a shift of the peak of Ib stage to younger age in the two commune aggregates mentioned. The question is whether this shift of the peak of Ib stage could be an indicator of the unavoidable percentage of rapidly growing tumors in the population of SR Slovenia.